Abstract
Important developmental responses are elicited in neural stem and progenitor cells (NSPC) by activation of the receptor tyrosine kinases (RTK), including the fibroblast growth factor receptors, epidermal growth factor receptor, platelet-derived growth factor receptors and insulin-like growth factor receptor (IGF1R). Signalling through these RTK is necessary and sufficient for driving a number of developmental processes in the central nervous system. Within each of the four RTK families discussed here, receptors are activated by sets of ligands that do not cross-activate receptors of the other three families, and therefore, their activation can be independently regulated by ligand availability. These RTK pathways converge on a conserved core of signalling molecules, but differences between the receptors in utilisation of signalling molecules and molecular adaptors for intracellular signal propagation become increasingly apparent. Intracellular inhibitors of RTK signalling are widely involved in the regulation of developmental signalling in NSPC and often determine developmental outcomes of RTK activation. In addition, cellular responses of NSPC to the activation of a given RTK may be significantly modulated by signal strength. Cellular propensity to respond also plays a role in developmental outcomes of RTK signalling. In combination, these mechanisms regulate the balance between NSPC maintenance and differentiation during development and in adulthood. Attribution of particular developmental responses of NSPC to specific pathways of RTK signalling becomes increasingly elucidated. Co-activation of several RTK in developing NSPC is common, and analysis of co-operation between their signalling pathways may advance knowledge of RTK role in NSPC development.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
von Bohlen-und-Halbach O, Minichiello L, Unsicker K (2003) Haploinsufficiency in trkB and/or trkC neurotrophin receptors causes structural alterations in the aged hippocampus and amygdala. Eur J Neurosci 18(8):2319–2325
Silos-Santiago I, Fagan AM, Garber M, Fritzsch B, Barbacid M (1997) Severe sensory deficits but normal CNS development in newborn mice lacking TrkB and TrkC tyrosine protein kinase receptors. Eur J Neurosci 9(10):2045–2056
Wada T, Haigh JJ, Ema M, Hitoshi S, Chaddah R, Rossant J, Nagy A, van der Kooy D (2006) Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. J Neurosci 26(25):6803–6812
Calvo CF, Fontaine RH, Soueid J, Tammela T, Makinen T, Alfaro-Cervello C, Bonnaud F, Miguez A, Benhaim L, Xu Y, Barallobre MJ, Moutkine I, Lyytikka J, Tatlisumak T, Pytowski B, Zalc B, Richardson W, Kessaris N, Garcia-Verdugo JM, Alitalo K, Eichmann A, Thomas JL (2011) Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis. Genes Dev 25(8):831–844. doi:10.1101/gad.615311
Wittko IM, Schanzer A, Kuzmichev A, Schneider FT, Shibuya M, Raab S, Plate KH (2009) VEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural progenitors in the rostral migratory stream in vivo. J Neurosci 29(27):8704–8714. doi:10.1523/jneurosci.5527-08.2009
Le Bras B, Barallobre MJ, Homman-Ludiye J, Ny A, Wyns S, Tammela T, Haiko P, Karkkainen MJ, Yuan L, Muriel MP, Chatzopoulou E, Breant C, Zalc B, Carmeliet P, Alitalo K, Eichmann A, Thomas JL (2006) VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci 9(3):340–348. doi:10.1038/nn1646
Coutu DL, Galipeau J (2011) Roles of FGF signaling in stem cell self-renewal, senescence and aging. Aging (Albany NY) 3(10):920–933
Ishibashi M, McMahon AP (2002) A sonic hedgehog-dependent signaling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryo. Development 129(20):4807–4819
Liu A, Li JY, Bromleigh C, Lao Z, Niswander LA, Joyner AL (2003) FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors. Development 130(25):6175–6185. doi:10.1242/dev.00845
Trokovic R, Trokovic N, Hernesniemi S, Pirvola U, Vogt Weisenhorn DM, Rossant J, McMahon AP, Wurst W, Partanen J (2003) FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals. EMBO J 22(8):1811–1823. doi:10.1093/emboj/cdg169
Blak AA, Naserke T, Weisenhorn DM, Prakash N, Partanen J, Wurst W (2005) Expression of Fgf receptors 1, 2, and 3 in the developing mid- and hindbrain of the mouse. Dev Dyn 233(3):1023–1030
Givol D, Yayon A (1992) Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. FASEB J 6(15):3362–3369
Yayon A, Zimmer Y, Shen GH, Avivi A, Yarden Y, Givol D (1992) A confined variable region confers ligand specificity on fibroblast growth factor receptors: implications for the origin of the immunoglobulin fold. EMBO J 11(5):1885–1890
Hecht D, Zimmerman N, Bedford M, Avivi A, Yayon A (1995) Identification of fibroblast growth factor 9 (FGF9) as a high affinity, heparin dependent ligand for FGF receptors 3 and 2 but not for FGF receptors 1 and 4. Growth Factors 12(3):223–233
Gómez-Pinilla F, Lee JW-K, Cotman CW (1994) Distribution of basic fibroblast growth factor in the developing rat brain. Neuroscience 61(4):911–923
Agasse F, Benzakour O, Berjeaud JM, Roger M, Coronas V (2006) Endogenous factors derived from embryonic cortex regulate proliferation and neuronal differentiation of postnatal subventricular zone cell cultures. Eur J Neurosci 23(8):1970–1976
Thisse B, Thisse C (2005) Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol 287(2):390–402
Itoh N, Ornitz DM (2004) Evolution of the Fgf and Fgfr gene families. Trends Genet 20(11):563–569
Ford-Perriss M, Abud H, Murphy M (2001) Fibroblast growth factors in the developing central nervous system. Clin Exp Pharmacol Physiol 28(7):493–503
Mason I (2007) Initiation to end point: the multiple roles of fibroblast growth factors in neural development. Nat Rev Neurosci 8(8):583–596. doi:10.1038/nrn2189
Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117–1134. doi:10.1016/j.cell.2010.06.011
Ronnstrand L, Heldin CH (2001) Mechanisms of platelet-derived growth factor-induced chemotaxis. Int J Cancer 91(6):757–762
Tallquist M, Kazlauskas A (2004) PDGF signaling in cells and mice. Cytokine Growth Factor Rev 15(4):205–213. doi:10.1016/j.cytogfr.2004.03.003
Ferguson KM, Berger MB, Mendrola JM, Cho H-S, Leahy DJ, Lemmon MA (2003) EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell 11(2):507–517
Mohammadi M, Olsen SK, Ibrahimi OA (2005) Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev 16(2):107–137. doi:10.1016/j.cytogfr.2005.01.008
Ward CW, Garrett TP (2004) Structural relationships between the insulin receptor and epidermal growth factor receptor families and other proteins. Curr Opin Drug Discov Devel 7(5):630–638
Oda K, Matsuoka Y, Funahashi A, Kitano H (2005) A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 1:2005–2010. doi:10.1038/msb4100014
Gordus A, Krall JA, Beyer EM, Kaushansky A, Wolf-Yadlin A, Sevecka M, Chang BH, Rush J, MacBeath G (2009) Linear combinations of docking affinities explain quantitative differences in RTK signaling. Mol Syst Biol 5:235. doi:10.1038/msb.2008.72
Martin B, Brenneman R, Golden E, Walent T, Becker KG, Prabhu VV, Wood W 3rd, Ladenheim B, Cadet JL, Maudsley S (2009) Growth factor signals in neural cells: coherent patterns of interaction control multiple levels of molecular and phenotypic responses. J Biol Chem 284(4):2493–2511. doi:10.1074/jbc.M804545200
Choi DY, Toledo-Aral JJ, Lin HY, Ischenko I, Medina L, Safo P, Mandel G, Levinson SR, Halegoua S, Hayman MJ (2001) Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction pathways. J Biol Chem 276(7):5116–5122
Luo Y, Yang C, Jin C, Xie R, Wang F, McKeehan WL (2009) Novel phosphotyrosine targets of FGFR2IIIb signaling. Cell Signal 21(9):1370–1378. doi:10.1016/j.cellsig.2009.04.004
Siddle K (2012) Molecular basis of signaling specificity of insulin and IGF receptors: neglected corners and recent advances. Front Endocrinol (Lausanne) 3:34. doi:10.3389/fendo.2012.00034
Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, Christensen ST (2005) PDGFRaa signaling is regulated through the primary cilium in fibroblasts. Curr Biol 15(20):1861–1866. doi:10.1016/j.cub.2005.09.012
Klinghoffer RA, Hamilton TG, Hoch R, Soriano P (2002) An allelic series at the PDGFaR locus indicates unequal contributions of distinct signaling pathways during development. Dev Cell 2(1):103–113
Tallquist MD, Klinghoffer RA, Heuchel R, Mueting-Nelsen PF, Corrin PD, Heldin CH, Johnson RJ, Soriano P (2000) Retention of PDGFR-b function in mice in the absence of phosphatidylinositol 3′-kinase and phospholipase Cg signaling pathways. Genes Dev 14(24):3179–3190
Liu BA, Engelmann BW, Jablonowski K, Higginbotham K, Stergachis AB, Nash PD (2012) SRC homology 2 domain binding sites in insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome. Cell Commun Signal 10(1):27. doi:10.1186/1478-811x-10-27
Witzel F, Maddison L, Bluthgen N (2012) How scaffolds shape MAPK signaling: what we know and opportunities for systems approaches. Front Physiol 3:475. doi:10.3389/fphys.2012.00475
Kutateladze TG (2010) Translation of the phosphoinositide code by PI effectors. Nat Chem Biol 6(7):507–513. doi:10.1038/nchembio.390
Marone R, Cmiljanovic V, Giese B, Wymann MP (2008) Targeting phosphoinositide 3-kinase: moving towards therapy. Biochim Biophys Acta 1784(1):159–185. doi:10.1016/j.bbapap.2007.10.003
DiNitto JP, Lambright DG (2006) Membrane and juxtamembrane targeting by PH and PTB domains. Biochim Biophys Acta 1761(8):850–867. doi:10.1016/j.bbalip.2006.04.008
Rodrigues GA, Falasca M, Zhang Z, Ong SH, Schlessinger J (2000) A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling. Mol Cell Biol 20(4):1448–1459
Novosyadlyy R, Dudas J, Pannem R, Ramadori G, Scharf JG (2006) Crosstalk between PDGF and IGF-I receptors in rat liver myofibroblasts: implication for liver fibrogenesis. Lab Invest 86(7):710–723. doi:10.1038/labinvest.3700426
Brummer T, Schmitz-Peiffer C, Daly RJ (2010) Docking proteins. FEBS J 277(21):4356–4369. doi:10.1111/j.1742-4658.2010.07865.x
Harlan JE, Hajduk PJ, Yoon HS, Fesik SW (1994) Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature 371(6493):168–170. doi:10.1038/371168a0
Uhlik MT, Temple B, Bencharit S, Kimple AJ, Siderovski DP, Johnson GL (2005) Structural and evolutionary division of phosphotyrosine binding (PTB) domains. J Mol Biol 345(1):1–20. doi:10.1016/j.jmb.2004.10.038
Forman-Kay JD, Pawson T (1999) Diversity in protein recognition by PTB domains. Curr Opin Struct Biol 9(6):690–695
George R, Schuller AC, Harris R, Ladbury JE (2008) A phosphorylation-dependent gating mechanism controls the SH2 domain interactions of the Shc adaptor protein. J Mol Biol 377(3):740–747. doi:10.1016/j.jmb.2007.12.040
Gotoh N (2008) Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins. Cancer Sci 99(7):1319–1325. doi:10.1111/j.1349-7006.2008.00840.x
Huang L, Watanabe M, Chikamori M, Kido Y, Yamamoto T, Shibuya M, Gotoh N, Tsuchida N (2006) Unique role of SNT-2/FRS2b/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways. Oncogene 25(49):6457–6466. doi:10.1038/sj.onc.1209656
Xu X, Weinstein M, Li C, Naski M, Cohen RI, Ornitz DM, Leder P, Deng C (1998) Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125(4):753–765
Zhang Y, McKeehan K, Lin Y, Zhang J, Wang F (2008) Fibroblast growth factor receptor 1 (FGFR1) tyrosine phosphorylation regulates binding of FGFR substrate 2a (FRS2a) but not FRS2 to the receptor. Mol Endocrinol 22(1):167–175
Hadari YR, Gotoh N, Kouhara H, Lax I, Schlessinger J (2001) Critical role for the docking-protein FRS2 a in FGF receptor-mediated signal transduction pathways. Proc Natl Acad Sci U S A 98(15):8578–8583. doi:10.1073/pnas.161259898
Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I (2001) Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci U S A 98(11):6074–6079. doi:10.1073/pnas.111114298
Tomasovic A, Traub S, Tikkanen R (2012) Molecular networks in FGF signaling: flotillin-1 and cbl-associated protein compete for the binding to fibroblast growth factor receptor substrate 2. PLoS One 7(1):e29739. doi:10.1371/journal.pone.0029739
Hoch RV, Soriano P (2006) Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Development 133(4):663–673
Gotoh N, Manova K, Tanaka S, Murohashi M, Hadari Y, Lee A, Hamada Y, Hiroe T, Ito M, Kurihara T, Nakazato H, Shibuya M, Lax I, Lacy E, Schlessinger J (2005) The docking protein FRS2a is an essential component of multiple fibroblast growth factor responses during early mouse development. Mol Cell Biol 25(10):4105–4116. doi:10.1128/mcb.25.10.4105-4116.2005
Hryciw T, MacDonald JI, Phillips R, Seah C, Pasternak S, Meakin SO (2010) The fibroblast growth factor receptor substrate 3 adapter is a developmentally regulated microtubule-associated protein expressed in migrating and differentiated neurons. J Neurochem 112(4):924–939. doi:10.1111/j.1471-4159.2009.06503.x
Ye P, D’Ercole AJ (2006) Insulin-like growth factor actions during development of neural stem cells and progenitors in the central nervous system. J Neurosci Res 83(1):1–6
Freude S, Leeser U, Muller M, Hettich MM, Udelhoven M, Schilbach K, Tobe K, Kadowaki T, Kohler C, Schroder H, Krone W, Bruning JC, Schubert M (2008) IRS-2 branch of IGF-1 receptor signaling is essential for appropriate timing of myelination. J Neurochem 107(4):907–917
Ye P, Li L, Lund PK, D’Ercole AJ (2002) Deficient expression of insulin receptor substrate-1 (IRS-1) fails to block insulin-like growth factor-I (IGF-I) stimulation of brain growth and myelination. Brain Res Dev Brain Res 136(2):111–121
Hanke S, Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. Mol Cell Proteomics 8(3):519–534. doi:10.1074/mcp.M800407-MCP200
Schubert M, Brazil DP, Burks DJ, Kushner JA, Ye J, Flint CL, Farhang-Fallah J, Dikkes P, Warot XM, Rio C, Corfas G, White MF (2003) Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci 23(18):7084–7092
Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hayakawa T, Terauchi Y, Ueki K, Kaburagi Y, Satoh S et al (1994) Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372(6502):182–186. doi:10.1038/372182a0
Wohrle FU, Daly RJ, Brummer T (2009) Function, regulation and pathological roles of the Gab/DOS docking proteins. Cell Commun Signal 7:22. doi:10.1186/1478-811x-7-22
Rozakis-Adcock M, McGlade J, Mbamalu G, Pelicci G, Daly R, Li W, Batzer A, Thomas S, Brugge J, Pelicci PG et al (1992) Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases. Nature 360(6405):689–692. doi:10.1038/360689a0
Harkiolaki M, Tsirka T, Lewitzky M, Simister PC, Joshi D, Bird LE, Jones EY, O’Reilly N, Feller SM (2009) Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. Structure 17(6):809–822. doi:10.1016/j.str.2009.03.017
Terasawa H, Kohda D, Hatanaka H, Tsuchiya S, Ogura K, Nagata K, Ishii S, Mandiyan V, Ullrich A, Schlessinger J et al (1994) Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos. Nat Struct Biol 1(12):891–897
McDonald CB, Seldeen KL, Deegan BJ, Bhat V, Farooq A (2010) Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control. Arch Biochem Biophys 494(2):216–225. doi:10.1016/j.abb.2009.12.011
McDonald CB, Seldeen KL, Deegan BJ, Bhat V, Farooq A (2011) Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms. J Mol Recognit 24(4):585–596. doi:10.1002/jmr.1080
Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW (2003) Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284(1):31–53
Li W, Nishimura R, Kashishian A, Batzer AG, Kim WJ, Cooper JA, Schlessinger J (1994) A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase. Mol Cell Biol 14(1):509–517
Mattoon DR, Lamothe B, Lax I, Schlessinger J (2004) The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. BMC Biol 2:24. doi:10.1186/1741-7007-2-24
Lamothe B, Yamada M, Schaeper U, Birchmeier W, Lax I, Schlessinger J (2004) The docking protein Gab1 is an essential component of an indirect mechanism for fibroblast growth factor stimulation of the phosphatidylinositol 3-kinase/Akt antiapoptotic pathway. Mol Cell Biol 24(13):5657–5666. doi:10.1128/mcb.24.13.5657-5666.2004
Mao Y, Lee AW (2005) A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid-induced neuronal differentiation. J Cell Biol 170(2):305–316
Hayakawa-Yano Y, Nishida K, Fukami S, Gotoh Y, Hirano T, Nakagawa T, Shimazaki T, Okano H (2007) Epidermal growth factor signaling mediated by grb2 associated binder1 is required for the spatiotemporally regulated proliferation of olig2-expressing progenitors in the embryonic spinal cord. Stem Cells 25(6):1410–1422
Schaeper U, Vogel R, Chmielowiec J, Huelsken J, Rosario M, Birchmeier W (2007) Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Proc Natl Acad Sci U S A 104(39):15376–15381. doi:10.1073/pnas.0702555104
Roshan B, Kjelsberg C, Spokes K, Eldred A, Crovello CS, Cantley LG (1999) Activated ERK2 interacts with and phosphorylates the docking protein GAB1. J Biol Chem 274(51):36362–36368
Lynch DK, Daly RJ (2002) PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2. EMBO J 21(1–2):72–82
Brummer T, Larance M, Herrera Abreu MT, Lyons RJ, Timpson P, Emmerich CH, Fleuren ED, Lehrbach GM, Schramek D, Guilhaus M, James DE, Daly RJ (2008) Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. EMBO J 27(17):2305–2316
Itoh M, Yoshida Y, Nishida K, Narimatsu M, Hibi M, Hirano T (2000) Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol Cell Biol 20(10):3695–3704
Nishida K, Hirano T (2003) The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci 94(12):1029–1033
Ravichandran KS (2001) Signaling via Shc family adapter proteins. Oncogene 20(44):6322–6330. doi:10.1038/sj.onc.1204776
Sweet DT, Tzima E (2009) Spatial signaling networks converge at the adaptor protein Shc. Cell Cycle 8(2):231–235
Migliaccio E, Mele S, Salcini AE, Pelicci G, Lai KM, Superti-Furga G, Pawson T, Di Fiore PP, Lanfrancone L, Pelicci PG (1997) Opposite effects of the p52shc/p46shc and p66shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway. EMBO J 16(4):706–716. doi:10.1093/emboj/16.4.706
Bonfini L, Migliaccio E, Pelicci G, Lanfrancone L, Pelicci PG (1996) Not all Shc’s roads lead to Ras. Trends Biochem Sci 21(7):257–261
Radhakrishnan Y, Maile LA, Ling Y, Graves LM, Clemmons DR (2008) Insulin-like growth factor-I stimulates Shc-dependent phosphatidylinositol 3-kinase activation via Grb2-associated p85 in vascular smooth muscle cells. J Biol Chem 283(24):16320–16331. doi:10.1074/jbc.M801687200
Smith MJ, Hardy WR, Li GY, Goudreault M, Hersch S, Metalnikov P, Starostine A, Pawson T, Ikura M (2010) The PTB domain of ShcA couples receptor activation to the cytoskeletal regulator IQGAP1. EMBO J 29(5):884–896. doi:10.1038/emboj.2009.399
Leahy M, Lyons A, Krause D, O’Connor R (2004) Impaired Shc, Ras, and MAPK activation but normal Akt activation in FL5.12 cells expressing an insulin-like growth factor I receptor mutated at tyrosines 1250 and 1251. J Biol Chem 279(18):18306–18313. doi:10.1074/jbc.M309234200
Woldt E, Matz RL, Terrand J, Mlih M, Gracia C, Foppolo S, Martin S, Bruban V, Ji J, Velot E, Herz J, Boucher P (2011) Differential signaling by adaptor molecules LRP1 and ShcA regulates adipogenesis by the insulin-like growth factor-1 receptor. J Biol Chem 286(19):16775–16782. doi:10.1074/jbc.M110.212878
Xi G, Shen X, Radhakrishnan Y, Maile L, Clemmons D (2010) Hyperglycemia-induced p66shc inhibits insulin-like growth factor I-dependent cell survival via impairment of Src kinase-mediated phosphoinositide-3 kinase/AKT activation in vascular smooth muscle cells. Endocrinology 151(8):3611–3623. doi:10.1210/en.2010-0242
Xi G, Shen X, Clemmons DR (2008) p66shc negatively regulates insulin-like growth factor I signal transduction via inhibition of p52shc binding to Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 leading to impaired growth factor receptor-bound protein-2 membrane recruitment. Mol Endocrinol 22(9):2162–2175. doi:10.1210/me.2008-0079
Arany I, Faisal A, Nagamine Y, Safirstein RL (2008) p66shc inhibits pro-survival epidermal growth factor receptor/ERK signaling during severe oxidative stress in mouse renal proximal tubule cells. J Biol Chem 283(10):6110–6117. doi:10.1074/jbc.M708799200
Papadimou E, Moiana A, Goffredo D, Koch P, Bertuzzi S, Brustle O, Cattaneo E, Conti L (2009) p66(ShcA) adaptor molecule accelerates ES cell neural induction. Mol Cell Neurosci 41(1):74–84. doi:10.1016/j.mcn.2009.01.010
Barua D, Faeder JR, Haugh JM (2007) Structure-based kinetic models of modular signaling protein function: focus on Shp2. Biophys J 92(7):2290–2300. doi:10.1529/biophysj.106.093484
Dance M, Montagner A, Salles JP, Yart A, Raynal P (2008) The molecular functions of Shp2 in the Ras/mitogen-activated protein kinase (ERK1/2) pathway. Cell Signal 20(3):453–459. doi:10.1016/j.cellsig.2007.10.002
Bennett AM, Tang TL, Sugimoto S, Walsh CT, Neel BG (1994) Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor b to Ras. Proc Natl Acad Sci U S A 91(15):7335–7339
Vogel W, Ullrich A (1996) Multiple in vivo phosphorylated tyrosine phosphatase SHP-2 engages binding to Grb2 via tyrosine 584. Cell Growth Differ 7(12):1589–1597
Shi ZQ, Yu DH, Park M, Marshall M, Feng GS (2000) Molecular mechanism for the Shp-2 tyrosine phosphatase function in promoting growth factor stimulation of Erk activity. Mol Cell Biol 20(5):1526–1536
Koyama T, Nakaoka Y, Fujio Y, Hirota H, Nishida K, Sugiyama S, Okamoto K, Yamauchi-Takihara K, Yoshimura M, Mochizuki S, Hori M, Hirano T, Mochizuki N (2008) Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway. J Biol Chem 283(35):24234–24244
Zagozdzon R, Kaminski R, Fu Y, Fu W, Bougeret C, Avraham HK (2006) Csk homologous kinase (CHK), unlike Csk, enhances MAPK activation via Ras-mediated signaling in a Src-independent manner. Cell Signal 18(6):871–881. doi:10.1016/j.cellsig.2005.07.016
Agazie YM, Hayman MJ (2003) Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling. Mol Cell Biol 23(21):7875–7886
Klinghoffer RA, Duckworth B, Valius M, Cantley L, Kazlauskas A (1996) Platelet-derived growth factor-dependent activation of phosphatidylinositol 3-kinase is regulated by receptor binding of SH2-domain-containing proteins which influence Ras activity. Mol Cell Biol 16(10):5905–5914
Montagner A, Yart A, Dance M, Perret B, Salles JP, Raynal P (2005) A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation. J Biol Chem 280(7):5350–5360. doi:10.1074/jbc.M410012200
Quintanar-Audelo M, Yusoff P, Sinniah S, Chandramouli S, Guy GR (2011) Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein (SPRED1), a tyrosine-protein phosphatase non-receptor type 11 (SHP2) substrate in the Ras/extracellular signal-regulated kinase (ERK) pathway. J Biol Chem 286(26):23102–23112. doi:10.1074/jbc.M110.212662
Saxton TM, Henkemeyer M, Gasca S, Shen R, Rossi DJ, Shalaby F, Feng GS, Pawson T (1997) Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. EMBO J 16(9):2352–2364. doi:10.1093/emboj/16.9.2352
Raman M, Chen W, Cobb MH (2007) Differential regulation and properties of MAPKs. Oncogene 26(22):3100–3112. doi:10.1038/sj.onc.1210392
Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75(1):50–83. doi:10.1128/mmbr.00031-10
Lefloch R, Pouyssegur J, Lenormand P (2008) Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels. Mol Cell Biol 28(1):511–527. doi:10.1128/mcb.00800-07
Imamura O, Satoh Y, Endo S, Takishima K (2008) Analysis of ERK2 function in neural stem/progenitor cells via nervous system-specific gene disruption. Stem Cells 26(12):3247-56
Wortzel I, Seger R (2011) The ERK cascade: distinct functions within various subcellular organelles. Genes Cancer 2(3):195–209. doi:10.1177/1947601911407328
Yip-Schneider MT, Miao W, Lin A, Barnard DS, Tzivion G, Marshall MS (2000) Regulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association. Biochem J 351(Pt 1):151–159
Molzan M, Schumacher B, Ottmann C, Baljuls A, Polzien L, Weyand M, Thiel P, Rose R, Rose M, Kuhenne P, Kaiser M, Rapp UR, Kuhlmann J (2010) Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling. Mol Cell Biol 30(19):4698–4711. doi:10.1128/mcb.01636-09
Fehrenbacher N, Bar-Sagi D, Philips M (2009) Ras/MAPK signaling from endomembranes. Mol Oncol 3(4):297–307. doi:10.1016/j.molonc.2009.06.004
Lorenz K, Schmitt JP, Schmitteckert EM, Lohse MJ (2009) A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy. Nat Med 15(1):75–83. doi:10.1038/nm.1893
Chuderland D, Konson A, Seger R (2008) Identification and characterization of a general nuclear translocation signal in signaling proteins. Mol Cell 31(6):850–861. doi:10.1016/j.molcel.2008.08.007
Lidke DS, Huang F, Post JN, Rieger B, Wilsbacher J, Thomas JL, Pouyssegur J, Jovin TM, Lenormand P (2010) ERK nuclear translocation is dimerization-independent but controlled by the rate of phosphorylation. J Biol Chem 285(5):3092–3102. doi:10.1074/jbc.M109.064972
von Kriegsheim A, Baiocchi D, Birtwistle M, Sumpton D, Bienvenut W, Morrice N, Yamada K, Lamond A, Kalna G, Orton R, Gilbert D, Kolch W (2009) Cell fate decisions are specified by the dynamic ERK interactome. Nat Cell Biol 11(12):1458–1464. doi:10.1038/ncb1994
Hughes R, Gilley J, Kristiansen M, Ham J (2011) The MEK-ERK pathway negatively regulates bim expression through the 3′ UTR in sympathetic neurons. BMC Neurosci 12:69. doi:10.1186/1471-2202-12-69
Wang CC, Cirit M, Haugh JM (2009) PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk. Mol Syst Biol 5:246. doi:10.1038/msb.2009.4
Castellano E, Downward J (2011) RAS interaction with PI3K: more than just another effector pathway. Genes Cancer 2(3):261–274. doi:10.1177/1947601911408079
Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, Roche S, Payrastre B, Chap H, Raynal P (2001) A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor. J Biol Chem 276(12):8856–8864. doi:10.1074/jbc.M006966200
Sampaio C, Dance M, Montagner A, Edouard T, Malet N, Perret B, Yart A, Salles JP, Raynal P (2008) Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 activation via differential Gab1/Shp2 recruitment: consequences for resistance to epidermal growth factor receptor inhibition. Mol Cell Biol 28(2):587–600. doi:10.1128/mcb.01318-07
Wennstrom S, Downward J (1999) Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor. Mol Cell Biol 19(6):4279–4288
Currie RA, Walker KS, Gray A, Deak M, Casamayor A, Downes CP, Cohen P, Alessi DR, Lucocq J (1999) Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1. Biochem J 337(Pt 3):575–583
Nakamura A, Naito M, Tsuruo T, Fujita N (2008) Freud-1/Aki1, a novel PDK1-interacting protein, functions as a scaffold to activate the PDK1/Akt pathway in epidermal growth factor signaling. Mol Cell Biol 28(19):5996–6009. doi:10.1128/mcb.00114-08
Shen X, Xi G, Radhakrishnan Y, Clemmons DR (2010) PDK1 recruitment to the SHPS-1 signaling complex enhances insulin-like growth factor-i-stimulated AKT activation and vascular smooth muscle cell survival. J Biol Chem 285(38):29416–29424. doi:10.1074/jbc.M110.155325
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307(5712):1098–1101. doi:10.1126/science.1106148
Weber JD, Gutmann DH (2012) Deconvoluting mTOR biology. Cell Cycle 11(2):236–248. doi:10.4161/cc.11.2.19022
Chen CH, dos Sarbassov D (2011) The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2. J Biol Chem 286(46):40386–40394. doi:10.1074/jbc.M111.282590
Glidden EJ, Gray LG, Vemuru S, Li D, Harris TE, Mayo MW (2012) Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt protein. J Biol Chem 287(1):581–588. doi:10.1074/jbc.M111.304337
Su B, Jacinto E (2011) Mammalian TOR signaling to the AGC kinases. Crit Rev Biochem Mol Biol 46(6):527–547. doi:10.3109/10409238.2011.618113
Schmidt-Strassburger U, Schips TG, Maier HJ, Kloiber K, Mannella F, Braunstein KE, Holzmann K, Ushmorov A, Liebau S, Boeckers TM, Wirth T (2012) Expression of constitutively active FoxO3 in murine forebrain leads to a loss of neural progenitors. FASEB J 26(12):4990–5001. doi:10.1096/fj.12-208587
Pearce LR, Komander D, Alessi DR (2010) The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol 11(1):9–22. doi:10.1038/nrm2822
Han JM, Sahin M (2011) TSC1/TSC2 signaling in the CNS. FEBS Lett 585(7):973–980. doi:10.1016/j.febslet.2011.02.001
Maffucci T, Raimondi C, Abu-Hayyeh S, Dominguez V, Sala G, Zachary I, Falasca M (2009) A phosphoinositide 3-kinase/phospholipase Cg1 pathway regulates fibroblast growth factor-induced capillary tube formation. PLoS One 4(12):e8285. doi:10.1371/journal.pone.0008285
Edwin F, Anderson K, Ying C, Patel TB (2009) Intermolecular interactions of Sprouty proteins and their implications in development and disease. Mol Pharmacol 76(4):679–691. doi:10.1124/mol.109.055848
Cabrita MA, Christofori G (2008) Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis 11(1):53–62. doi:10.1007/s10456-008-9089-1
Mason JM, Morrison DJ, Basson MA, Licht JD (2006) Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends Cell Biol 16(1):45–54
Chow SY, Yu CY, Guy GR (2009) Sprouty2 interacts with protein kinase C d and disrupts phosphorylation of protein kinase D1. J Biol Chem 284(29):19623–19636. doi:10.1074/jbc.M109.021600
Akbulut S, Reddi AL, Aggarwal P, Ambardekar C, Canciani B, Kim MK, Hix L, Vilimas T, Mason J, Basson MA, Lovatt M, Powell J, Collins S, Quatela S, Phillips M, Licht JD (2010) Sprouty proteins inhibit receptor-mediated activation of phosphatidylinositol-specific phospholipase C. Mol Biol Cell 21(19):3487–3496. doi:10.1091/mbc.E10-02-0123
Lim J, Wong ES, Ong SH, Yusoff P, Low BC, Guy GR (2000) Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. J Biol Chem 275(42):32837–32845. doi:10.1074/jbc.M002156200
Yigzaw Y, Cartin L, Pierre S, Scholich K, Patel TB (2001) The C terminus of sprouty is important for modulation of cellular migration and proliferation. J Biol Chem 276(25):22742–22747. doi:10.1074/jbc.M100123200
Mason JM, Morrison DJ, Bassit B, Dimri M, Band H, Licht JD, Gross I (2004) Tyrosine phosphorylation of Sprouty proteins regulates their ability to inhibit growth factor signaling: a dual feedback loop. Mol Biol Cell 15(5):2176–2188. doi:10.1091/mbc.E03-07-0503
Alsina FC, Irala D, Fontanet PA, Hita FJ, Ledda F, Paratcha G (2012) Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF. PLoS One 7(2):e32087. doi:10.1371/journal.pone.0032087
Hanafusa H, Torii S, Yasunaga T, Nishida E (2002) Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Nat Cell Biol 4(11):850–858. doi:10.1038/ncb867
Abe M, Naski MC (2004) Regulation of sprouty expression by PLCg and calcium-dependent signals. Biochem Biophys Res Commun 323(3):1040–1047. doi:10.1016/j.bbrc.2004.08.198
Sasaki A, Taketomi T, Wakioka T, Kato R, Yoshimura A (2001) Identification of a dominant negative mutant of Sprouty that potentiates fibroblast growth factor- but not epidermal growth factor-induced ERK activation. J Biol Chem 276(39):36804–36808. doi:10.1074/jbc.C100386200
Wong ES, Fong CW, Lim J, Yusoff P, Low BC, Langdon WY, Guy GR (2002) Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling. EMBO J 21(18):4796–4808
Edwin F, Patel TB (2008) A novel role of Sprouty 2 in regulating cellular apoptosis. J Biol Chem 283(6):3181–3190. doi:10.1074/jbc.M706567200
Edwin F, Singh R, Endersby R, Baker SJ, Patel TB (2006) The tumor suppressor PTEN is necessary for human Sprouty 2-mediated inhibition of cell proliferation. J Biol Chem 281(8):4816–4822. doi:10.1074/jbc.M508300200
Edwin F, Anderson K, Patel TB (2010) HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2. J Biol Chem 285(1):255–264. doi:10.1074/jbc.M109.030882
DaSilva J, Xu L, Kim HJ, Miller WT, Bar-Sagi D (2006) Regulation of sprouty stability by Mnk1-dependent phosphorylation. Mol Cell Biol 26(5):1898–1907. doi:10.1128/mcb.26.5.1898-1907.2006
Aranda S, Alvarez M, Turro S, Laguna A, de la Luna S (2008) Sprouty2-mediated inhibition of fibroblast growth factor signaling is modulated by the protein kinase DYRK1A. Mol Cell Biol 28(19):5899–5911. doi:10.1128/mcb.00394-08
Katoh Y, Katoh M (2006) FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells. Int J Mol Med 17(3):529–532
Hayashi S, Shimoda T, Nakajima M, Tsukada Y, Sakumura Y, Dale JK, Maroto M, Kohno K, Matsui T, Bessho Y (2009) Sprouty4, an FGF inhibitor, displays cyclic gene expression under the control of the notch segmentation clock in the mouse PSM. PLoS One 4(5):e5603. doi:10.1371/journal.pone.0005603
Shim K, Minowada G, Coling DE, Martin GR (2005) Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Dev Cell 8(4):553–564. doi:10.1016/j.devcel.2005.02.009
Simrick S, Lickert H, Basson MA (2011) Sprouty genes are essential for the normal development of epibranchial ganglia in the mouse embryo. Dev Biol 358(1):147–155. doi:10.1016/j.ydbio.2011.07.024
Taketomi T, Yoshiga D, Taniguchi K, Kobayashi T, Nonami A, Kato R, Sasaki M, Sasaki A, Ishibashi H, Moriyama M, Nakamura K, Nishimura J, Yoshimura A (2005) Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nat Neurosci 8(7):855–857. doi:10.1038/nn1485
Yang X, Harkins LK, Zubanova O, Harrington A, Kovalenko D, Nadeau RJ, Chen PY, Toher JL, Lindner V, Liaw L, Friesel R (2008) Overexpression of Spry1 in chondrocytes causes attenuated FGFR ubiquitination and sustained ERK activation resulting in chondrodysplasia. Dev Biol 321(1):64–76. doi:10.1016/j.ydbio.2008.05.555
de Alvaro C, Martinez N, Rojas JM, Lorenzo M (2005) Sprouty-2 overexpression in C2C12 cells confers myogenic differentiation properties in the presence of FGF2. Mol Biol Cell 16(9):4454–4461. doi:10.1091/mbc.E05-05-0419
Bundschu K, Walter U, Schuh K (2007) Getting a first clue about SPRED functions. Bioessays 29(9):897–907. doi:10.1002/bies.20632
Kato R, Nonami A, Taketomi T, Wakioka T, Kuroiwa A, Matsuda Y, Yoshimura A (2003) Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation. Biochem Biophys Res Commun 302(4):767–772
Bundschu K, Walter U, Schuh K (2006) The VASP-Spred-Sprouty domain puzzle. J Biol Chem 281(48):36477–36481. doi:10.1074/jbc.R600023200
Tuduce IL, Schuh K, Bundschu K (2010) Spred2 expression during mouse development. Dev Dyn 239(11):3072–3085. doi:10.1002/dvdy.22432
Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, Tsuneoka M, Komiya S, Baron R, Yoshimura A (2001) Spred is a Sprouty-related suppressor of Ras signalling. Nature 412(6847):647–651. doi:10.1038/35088082
King JA, Straffon AF, D’Abaco GM, Poon CL, ST I, Smith CM, Buchert M, Corcoran NM, Hall NE, Callus BA, Sarcevic B, Martin D, Lock P, Hovens CM (2005) Distinct requirements for the Sprouty domain for functional activity of Spred proteins. Biochem J 388(Pt 2):445–454. doi:10.1042/bj20041284
Mardakheh FK, Yekezare M, Machesky LM, Heath JK (2009) Spred2 interaction with the late endosomal protein NBR1 down-regulates fibroblast growth factor receptor signaling. J Cell Biol 187(2):265–277. doi:10.1083/jcb.200905118
Li D, Jackson RA, Yusoff P, Guy GR (2010) Direct association of Sprouty-related protein with an EVH1 domain (SPRED) 1 or SPRED2 with DYRK1A modifies substrate/kinase interactions. J Biol Chem 285(46):35374–35385. doi:10.1074/jbc.M110.148445
Ullrich M, Bundschu K, Benz PM, Abesser M, Freudinger R, Fischer T, Ullrich J, Renne T, Walter U, Schuh K (2011) Identification of SPRED2 (sprouty-related protein with EVH1 domain 2) as a negative regulator of the hypothalamic-pituitary-adrenal axis. J Biol Chem 286(11):9477–9488. doi:10.1074/jbc.M110.171306
Sun H, Charles CH, Lau LF, Tonks NK (1993) MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell 75(3):487–493
Jeffrey KL, Camps M, Rommel C, Mackay CR (2007) Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 6(5):391–403. doi:10.1038/nrd2289
Owens DM, Keyse SM (2007) Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases. Oncogene 26(22):3203–3213. doi:10.1038/sj.onc.1210412
Caunt CJ, Rivers CA, Conway-Campbell BL, Norman MR, McArdle CA (2008) Epidermal growth factor receptor and protein kinase C signaling to ERK2: spatiotemporal regulation of ERK2 by dual specificity phosphatases. J Biol Chem 283(10):6241–6252. doi:10.1074/jbc.M706624200
Dickinson RJ, Eblaghie MC, Keyse SM, Morriss-Kay GM (2002) Expression of the ERK-specific MAP kinase phosphatase PYST1/MKP3 in mouse embryos during morphogenesis and early organogenesis. Mech Dev 113(2):193–196
Li C, Scott DA, Hatch E, Tian X, Mansour SL (2007) Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development. Development 134(1):167–176. doi:10.1242/dev.02701
Karlsson M, Mathers J, Dickinson RJ, Mandl M, Keyse SM (2004) Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal. J Biol Chem 279(40):41882–41891. doi:10.1074/jbc.M406720200
Nichols A, Camps M, Gillieron C, Chabert C, Brunet A, Wilsbacher J, Cobb M, Pouyssegur J, Shaw JP, Arkinstall S (2000) Substrate recognition domains within extracellular signal-regulated kinase mediate binding and catalytic activation of mitogen-activated protein kinase phosphatase-3. J Biol Chem 275(32):24613–24621. doi:10.1074/jbc.M001515200
Mark JK, Aubin RA, Smith S, Hefford MA (2008) Inhibition of mitogen-activated protein kinase phosphatase 3 activity by interdomain binding. J Biol Chem 283(42):28574–28583. doi:10.1074/jbc.M801747200
Ekerot M, Stavridis MP, Delavaine L, Mitchell MP, Staples C, Owens DM, Keenan ID, Dickinson RJ, Storey KG, Keyse SM (2008) Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter. Biochem J 412(2):287–298. doi:10.1042/bj20071512
Echevarria D, Martinez S, Marques S, Lucas-Teixeira V, Belo JA (2005) Mkp3 is a negative feedback modulator of Fgf8 signaling in the mammalian isthmic organizer. Dev Biol 277(1):114–128. doi:10.1016/j.ydbio.2004.09.011
Nichols J, Silva J, Roode M, Smith A (2009) Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development 136(19):3215–3222. doi:10.1242/dev.038893
Lavaute TM, Yoo YD, Pankratz MT, Weick JP, Gerstner JR, Zhang SC (2009) Regulation of neural specification from human embryonic stem cells by BMP and FGF. Stem Cells 27(8):1741–1749
Kunath T, Saba-El-Leil MK, Almousailleakh M, Wray J, Meloche S, Smith A (2007) FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development 134(16):2895–2902
Jung JE, Moon SH, Kim DK, Choi C, Song J, Park KS (2012) Sprouty1 regulates neural and endothelial differentiation of mouse embryonic stem cells. Stem Cells Dev 21(4):554–561. doi:10.1089/scd.2011.0110
Greber B, Coulon P, Zhang M, Moritz S, Frank S, Muller-Molina AJ, Arauzo-Bravo MJ, Han DW, Pape HC, Scholer HR (2011) FGF signalling inhibits neural induction in human embryonic stem cells. EMBO J 30(24):4874–4884. doi:10.1038/emboj.2011.407
Stavridis MP, Collins BJ, Storey KG (2010) Retinoic acid orchestrates fibroblast growth factor signalling to drive embryonic stem cell differentiation. Development 137(6):881–890. doi:10.1242/dev.043117
Hitoshi S, Seaberg RM, Koscik C, Alexson T, Kusunoki S, Kanazawa I, Tsuji S, van der Kooy D (2004) Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling. Genes Dev 18(15):1806–1811. doi:10.1101/gad.1208404
Smukler SR, Runciman SB, Xu S, van der Kooy D (2006) Embryonic stem cells assume a primitive neural stem cell fate in the absence of extrinsic influences. J Cell Biol 172(1):79–90
Tropepe V, Sibilia M, Ciruna BG, Rossant J, Wagner EF, van der Kooy D (1999) Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev Biol 208(1):166–188
Dang LT, Tropepe V (2010) FGF dependent regulation of Zfhx1b gene expression promotes the formation of definitive neural stem cells in the mouse anterior neurectoderm. Neural Dev 5:13. doi:10.1186/1749-8104-5-13
Ortega S, Ittmann M, Tsang SH, Ehrlich M, Basilico C (1998) Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2. Proc Natl Acad Sci U S A 95(10):5672–5677
Dono R, Texido G, Dussel R, Ehmke H, Zeller R (1998) Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. EMBO J 17(15):4213–4225. doi:10.1093/emboj/17.15.4213
Raballo R, Rhee J, Lyn-Cook R, Leckman JF, Schwartz ML, Vaccarino FM (2000) Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J Neurosci 20(13):5012–5023
Vaccarino FM, Schwartz ML, Raballo R, Nilsen J, Rhee J, Zhou M, Doetschman T, Coffin JD, Wyland JJ, Hung YT (1999) Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci 2(3):246–253. doi:10.1038/6350
Kalyani AJ, Mujtaba T, Rao MS (1999) Expression of EGF receptor and FGF receptor isoforms during neuroepithelial stem cell differentiation. J Neurobiol 38(2):207–224
Cai J, Wu Y, Mirua T, Pierce JL, Lucero MT, Albertine KH, Spangrude GJ, Rao MS (2002) Properties of a fetal multipotent neural stem cell (NEP cell). Dev Biol 251(2):221–240
Andrae J, Hansson I, Afink GB, Nister M (2001) Platelet-derived growth factor receptor-a in ventricular zone cells and in developing neurons. Mol Cell Neurosci 17(6):1001–1013. doi:10.1006/mcne.2001.0989
Noctor SC, Flint AC, Weissman TA, Wong WS, Clinton BK, Kriegstein AR (2002) Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J Neurosci 22 (8):3161–3173
Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7(2):136–144. doi:10.1038/nn1172
Gotz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6(10):777–788. doi:10.1038/nrm1739
Maric D, Fiorio Pla A, Chang YH, Barker JL (2007) Self-renewing and differentiating properties of cortical neural stem cells are selectively regulated by basic fibroblast growth factor (FGF) signaling via specific FGF receptors. J Neurosci 27(8):1836–1852
Yoon K, Nery S, Rutlin ML, Radtke F, Fishell G, Gaiano N (2004) Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors. J Neurosci 24(43):9497–9506. doi:10.1523/JNEUROSCI.0993-04.2004
Sahara S, O’Leary DD (2009) Fgf10 regulates transition period of cortical stem cell differentiation to radial glia controlling generation of neurons and basal progenitors. Neuron 63(1):48–62. doi:10.1016/j.neuron.2009.06.006
Miyata T, Kawaguchi A, Saito K, Kawano M, Muto T, Ogawa M (2004) Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131(13):3133–3145. doi:10.1242/dev.01173
Haubensak W, Attardo A, Denk W, Huttner WB (2004) Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A 101(9):3196–3201. doi:10.1073/pnas.0308600100
Yu X, Zecevic N (2011) Dorsal radial glial cells have the potential to generate cortical interneurons in human but not in mouse brain. J Neurosci 31(7):2413–2420. doi:10.1523/jneurosci.5249-10.2011
Mo Z, Moore AR, Filipovic R, Ogawa Y, Kazuhiro I, Antic SD, Zecevic N (2007) Human cortical neurons originate from radial glia and neuron-restricted progenitors. J Neurosci 27(15):4132–4145. doi:10.1523/jneurosci.0111-07.2007
Howard BM, Zhicheng M, Filipovic R, Moore AR, Antic SD, Zecevic N (2008) Radial glia cells in the developing human brain. Neuroscientist 14(5):459–473. doi:10.1177/1073858407313512
Ke Y, Zhang EE, Hagihara K, Wu D, Pang Y, Klein R, Curran T, Ranscht B, Feng GS (2007) Deletion of Shp2 in the brain leads to defective proliferation and differentiation in neural stem cells and early postnatal lethality. Mol Cell Biol 27(19):6706–6717
McFarland KN, Wilkes SR, Koss SE, Ravichandran KS, Mandell JW (2006) Neural-specific inactivation of ShcA results in increased embryonic neural progenitor apoptosis and microencephaly. J Neurosci 26(30):7885–7897
Phoenix TN, Temple S (2010) Spred1, a negative regulator of Ras-MAPK-ERK, is enriched in CNS germinal zones, dampens NSC proliferation, and maintains ventricular zone structure. Genes Dev 24(1):45–56. doi:10.1101/gad.1839510
Samuels IS, Karlo JC, Faruzzi AN, Pickering K, Herrup K, Sweatt JD, Saitta SC, Landreth GE (2008) Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function. J Neurosci 28(27):6983–6995. doi:10.1523/jneurosci.0679-08.2008
Kang W, Wong LC, Shi SH, Hebert JM (2009) The transition from radial glial to intermediate progenitor cell is inhibited by FGF signaling during corticogenesis. J Neurosci 29(46):14571–14580. doi:10.1523/jneurosci.3844-09.2009
McMillan EL, Kamps AL, Lake SS, Svendsen CN, Bhattacharyya A (2012) Gene expression changes in the MAPK pathway in both Fragile X and Down syndrome human neural progenitor cells. Am J Stem Cells 1(2):154–162
Chen J, Lai F, Niswander L (2012) The ubiquitin ligase mLin41 temporally promotes neural progenitor cell maintenance through FGF signaling. Genes Dev 26(8):803–815. doi:10.1101/gad.187641.112
Ohkubo Y, Uchida AO, Shin D, Partanen J, Vaccarino FM (2004) Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse. J Neurosci 24(27):6057–6069
Stevens HE, Smith KM, Maragnoli ME, Fagel D, Borok E, Shanabrough M, Horvath TL, Vaccarino FM (2010) Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J Neurosci 30(16):5590–5602. doi:10.1523/jneurosci.5837-09.2010
Caric D, Raphael H, Viti J, Feathers A, Wancio D, Lillien L (2001) EGFRs mediate chemotactic migration in the developing telencephalon. Development 128(21):4203–4216
Eagleson KL, Ferri RT, Levitt P (1996) Complementary distribution of collagen type IV and the epidermal growth factor receptor in the rat embryonic telencephalon. Cereb Cortex 6(3):540–549
Burrows RC, Wancio D, Levitt P, Lillien L (1997) Response diversity and the timing of progenitor cell maturation are regulated by developmental changes in EGFR expression in the cortex. Neuron 19(2):251–267
Lillien L, Gulacsi A (2006) Environmental signals elicit multiple responses in dorsal telencephalic progenitors by threshold-dependent mechanisms. Cereb Cortex 16(Suppl 1):i74–i81. doi:10.1093/cercor/bhj169
Ciccolini F, Mandl C, Holzl-Wenig G, Kehlenbach A, Hellwig A (2005) Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR. Dev Biol 284(1):112–125. doi:10.1016/j.ydbio.2005.05.007
Sinor-Anderson A, Lillien L (2011) Akt1 interacts with epidermal growth factor receptors and hedgehog signaling to increase stem/transit amplifying cells in the embryonic mouse cortex. Dev Neurobiol 71(9):759–771. doi:10.1002/dneu.20878
Jia H, Tao H, Feng R, Li M, Bai J, Sun T, Wen J, Hu Q (2011) Pax6 regulates the epidermal growth factor-responsive neural stem cells of the subventricular zone. Neuroreport 22(9):448–452. doi:10.1097/WNR.0b013e3283476b46
Hu Q, Zhang L, Wen J, Wang S, Li M, Feng R, Yang X, Li L (2010) The EGF receptor-sox2-EGF receptor feedback loop positively regulates the self-renewal of neural precursor cells. Stem Cells 28(2):279–286. doi:10.1002/stem.246
Vescovi AL, Reynolds BA, Fraser DD, Weiss S (1993) bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells. Neuron 11(5):951–966
Doe CQ, Goodman CS (1985) Early events in insect neurogenesis. II. The role of cell interactions and cell lineage in the determination of neuronal precursor cells. Dev Biol 111(1):206–219
Louvi A, Artavanis-Tsakonas S (2006) Notch signalling in vertebrate neural development. Nat Rev Neurosci 7(2):93–102
Mizutani K, Yoon K, Dang L, Tokunaga A, Gaiano N (2007) Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449(7160):351–355
Ishibashi M, Moriyoshi K, Sasai Y, Shiota K, Nakanishi S, Kageyama R (1994) Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system. EMBO J 13(8):1799–1805
Gaiano N, Nye JS, Fishell G (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26(2):395–404
Li H, Chang YW, Mohan K, Su HW, Ricupero CL, Baridi A, Hart RP, Grumet M (2008) Activated Notch1 maintains the phenotype of radial glial cells and promotes their adhesion to laminin by upregulating nidogen. Glia 56(6):646–658
Mason HA, Rakowiecki SM, Gridley T, Fishell G (2006) Loss of notch activity in the developing central nervous system leads to increased cell death. Dev Neurosci 28(1–2):49–57
Baek JH, Hatakeyama J, Sakamoto S, Ohtsuka T, Kageyama R (2006) Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system. Development 133(13):2467–2476. doi:10.1242/dev.02403
Nagao M, Sugimori M, Nakafuku M (2007) Cross talk between notch and growth factor/cytokine signaling pathways in neural stem cells. Mol Cell Biol 27(11):3982–3994. doi:10.1128/mcb.00170-07
Sato T, Shimazaki T, Naka H, Fukami S, Satoh Y, Okano H, Lax I, Schlessinger J, Gotoh N (2010) FRS2a regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells. Stem Cells 28(9):1661–1673. doi:10.1002/stem.488
Dang L, Yoon K, Wang M, Gaiano N (2006) Notch3 signaling promotes radial glial/progenitor character in the mammalian telencephalon. Dev Neurosci 28(1–2):58–69
Rotwein P, Burgess SK, Milbrandt JD, Krause JE (1988) Differential expression of insulin-like growth factor genes in rat central nervous system. Proc Natl Acad Sci U S A 85(1):265–269
Banks WA (2004) The source of cerebral insulin. Eur J Pharmacol 490(1–3):5–12. doi:10.1016/j.ejphar.2004.02.040
Schubert M, Gautam D, Surjo D, Ueki K, Baudler S, Schubert D, Kondo T, Alber J, Galldiks N, Kustermann E, Arndt S, Jacobs AH, Krone W, Kahn CR, Bruning JC (2004) Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A 101(9):3100–3105. doi:10.1073/pnas.0308724101
Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289(5487):2122–2125
Erickson RI, Paucar AA, Jackson RL, Visnyei K, Kornblum H (2008) Roles of insulin and transferrin in neural progenitor survival and proliferation. J Neurosci Res 86:1884–1894
Sessa A, Mao CA, Hadjantonakis AK, Klein WH, Broccoli V (2008) Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex. Neuron 60(1):56–69. doi:10.1016/j.neuron.2008.09.028
Kowalczyk T, Pontious A, Englund C, Daza RA, Bedogni F, Hodge R, Attardo A, Bell C, Huttner WB, Hevner RF (2009) Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb Cortex 19(10):2439–2450. doi:10.1093/cercor/bhn260
Kawaguchi D, Yoshimatsu T, Hozumi K, Gotoh Y (2008) Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon. Development 135(23):3849–3858
Gal JS, Morozov YM, Ayoub AE, Chatterjee M, Rakic P, Haydar TF (2006) Molecular and morphological heterogeneity of neural precursors in the mouse neocortical proliferative zones. J Neurosci 26(3):1045–1056
Sasaki S, Tabata H, Tachikawa K, Nakajima K (2008) The cortical subventricular zone-specific molecule Svet1 is part of the nuclear RNA coded by the putative netrin receptor gene Unc5d and is expressed in multipolar migrating cells. Mol Cell Neurosci 38(4):474–483. doi:10.1016/j.mcn.2008.04.002
Wang X, Tsai JW, LaMonica B, Kriegstein AR (2011) A new subtype of progenitor cell in the mouse embryonic neocortex. Nat Neurosci 14(5):555–561. doi:10.1038/nn.2807
Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E (2007) Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet 39(9):1120–1126. doi:10.1038/ng2113
Spurlock G, Bennett E, Chuzhanova N, Thomas N, Jim HP, Side L, Davies S, Haan E, Kerr B, Huson SM, Upadhyaya M (2009) SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. J Med Genet 46(7):431–437. doi:10.1136/jmg.2008.065474
Yamamoto S, Yoshino I, Shimazaki T, Murohashi M, Hevner RF, Lax I, Okano H, Shibuya M, Schlessinger J, Gotoh N (2005) Essential role of Shp2-binding sites on FRS2a for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells. Proc Natl Acad Sci U S A 102(44):15983–15988
Fyffe-Maricich SL, Karlo JC, Landreth GE, Miller RH (2011) The ERK2 mitogen-activated protein kinase regulates the timing of oligodendrocyte differentiation. J Neurosci 31(3):843–850. doi:10.1523/jneurosci.3239-10.2011
Gauthier AS, Furstoss O, Araki T, Chan R, Neel BG, Kaplan DR, Miller FD (2007) Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. Neuron 54(2):245–262. doi:10.1016/j.neuron.2007.03.027
Galabova-Kovacs G, Catalanotti F, Matzen D, Reyes GX, Zezula J, Herbst R, Silva A, Walter I, Baccarini M (2008) Essential role of B-Raf in oligodendrocyte maturation and myelination during postnatal central nervous system development. J Cell Biol 180(5):947–955
Menard C, Hein P, Paquin A, Savelson A, Yang XM, Lederfein D, Barnabe-Heider F, Mir AA, Sterneck E, Peterson AC, Johnson PF, Vinson C, Miller FD (2002) An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis. Neuron 36(4):597–610
Wang X, Tournier C (2006) Regulation of cellular functions by the ERK5 signalling pathway. Cell Signal 18(6):753–760. doi:10.1016/j.cellsig.2005.11.003
Hayashi M, Lee JD (2004) Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice. J Mol Med (Berl) 82(12):800–808. doi:10.1007/s00109-004-0602-8
Liu L, Cundiff P, Abel G, Wang Y, Faigle R, Sakagami H, Xu M, Xia Z (2006) Extracellular signal-regulated kinase (ERK) 5 is necessary and sufficient to specify cortical neuronal fate. Proc Natl Acad Sci U S A 103(25):9697–9702. doi:10.1073/pnas.0603373103
Cundiff P, Liu L, Wang Y, Zou J, Pan YW, Abel G, Duan X, Ming GL, Englund C, Hevner R, Xia Z (2009) ERK5 MAP kinase regulates neurogenin1 during cortical neurogenesis. PLoS One 4(4):e5204. doi:10.1371/journal.pone.0005204
Kornblum HI, Hussain R, Wiesen J, Miettinen P, Zurcher SD, Chow K, Derynck R, Werb Z (1998) Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor. J Neurosci Res 53(6):697–717
Sibilia M, Steinbach JP, Stingl L, Aguzzi A, Wagner EF (1998) A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor. EMBO J 17(3):719–731. doi:10.1093/emboj/17.3.719
Wagner B, Natarajan A, Grunaug S, Kroismayr R, Wagner EF, Sibilia M (2006) Neuronal survival depends on EGFR signaling in cortical but not midbrain astrocytes. EMBO J 25(4):752–762. doi:10.1038/sj.emboj.7600988
He F, Ge W, Martinowich K, Becker-Catania S, Coskun V, Zhu W, Wu H, Castro D, Guillemot F, Fan G, de Vellis J, Sun YE (2005) A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nat Neurosci 8(5):616–625. doi:10.1038/nn1440
Fishwick KJ, Li RA, Halley P, Deng P, Storey KG (2010) Initiation of neuronal differentiation requires PI3-kinase/TOR signalling in the vertebrate neural tube. Dev Biol 338(2):215–225. doi:10.1016/j.ydbio.2009.12.001
Oishi K, Watatani K, Itoh Y, Okano H, Guillemot F, Nakajima K, Gotoh Y (2009) Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1. Proc Natl Acad Sci U S A 106(31):13064–13069. doi:10.1073/pnas.0808400106
Ziegler AN, Schneider JS, Qin M, Tyler WA, Pintar JE, Fraidenraich D, Wood TL, Levison SW (2012) IGF-II promotes stemness of neural restricted precursors. Stem Cells 30(6):1265–1276. doi:10.1002/stem.1095
O’Leary DD, Sahara S (2008) Genetic regulation of arealization of the neocortex. Curr Opin Neurobiol 18(1):90–100. doi:10.1016/j.conb.2008.05.011
Tossell K, Kiecker C, Wizenmann A, Lang E, Irving C (2011) Notch signalling stabilises boundary formation at the midbrain-hindbrain organiser. Development 138(17):3745–3757. doi:10.1242/dev.070318
Hebert JM, Fishell G (2008) The genetics of early telencephalon patterning: some assembly required. Nat Rev Neurosci 9(9):678–685. doi:10.1038/nrn2463
Takahashi H, Liu FC (2006) Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors. Birth Defects Res C Embryo Today 78(3):256–266
Sansom SN, Hebert JM, Thammongkol U, Smith J, Nisbet G, Surani MA, McConnell SK, Livesey FJ (2005) Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap. Development 132(17):3947–3961. doi:10.1242/dev.01968
Gutin G, Fernandes M, Palazzolo L, Paek H, Yu K, Ornitz DM, McConnell SK, Hebert JM (2006) FGF signalling generates ventral telencephalic cells independently of SHH. Development 133(15):2937–2946
Shimamura K, Hartigan DJ, Martinez S, Puelles L, Rubenstein JL (1995) Longitudinal organization of the anterior neural plate and neural tube. Development 121(12):3923–3933
Danesin C, Houart C (2012) A Fox stops the Wnt: implications for forebrain development and diseases. Curr Opin Genet Dev 22(4):323–330. doi:10.1016/j.gde.2012.05.001
Houart C, Westerfield M, Wilson SW (1998) A small population of anterior cells patterns the forebrain during zebrafish gastrulation. Nature 391(6669):788–792. doi:10.1038/35853
Paek H, Gutin G, Hebert JM (2009) FGF signaling is strictly required to maintain early telencephalic precursor cell survival. Development 136(14):2457–2465. doi:10.1242/dev.032656
Regad T, Roth M, Bredenkamp N, Illing N, Papalopulu N (2007) The neural progenitor-specifying activity of FoxG1 is antagonistically regulated by CKI and FGF. Nat Cell Biol 9(5):531–540. doi:10.1038/ncb1573
Storm EE, Rubenstein JL, Martin GR (2003) Dosage of Fgf8 determines whether cell survival is positively or negatively regulated in the developing forebrain. Proc Natl Acad Sci U S A 100(4):1757–1762
Faedo A, Borello U, Rubenstein JL (2010) Repression of Fgf signaling by sprouty1-2 regulates cortical patterning in two distinct regions and times. J Neurosci 30(11):4015–4023. doi:10.1523/jneurosci.0307-10.2010
Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D (2011) Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J 30(16):3259–3273. doi:10.1038/emboj.2011.234
Hasegawa H, Ashigaki S, Takamatsu M, Suzuki-Migishima R, Ohbayashi N, Itoh N, Takada S, Tanabe Y (2004) Laminar patterning in the developing neocortex by temporally coordinated fibroblast growth factor signaling. J Neurosci 24(40):8711–8719
Hebert JM, Lin M, Partanen J, Rossant J, McConnell SK (2003) FGF signaling through FGFR1 is required for olfactory bulb morphogenesis. Development 130(6):1101–1111
Shin DM, Korada S, Raballo R, Shashikant CS, Simeone A, Taylor JR, Vaccarino F (2004) Loss of glutamatergic pyramidal neurons in frontal and temporal cortex resulting from attenuation of FGFR1 signaling is associated with spontaneous hyperactivity in mice. J Neurosci 24(9):2247–2258
Thomson RE, Kind PC, Graham NA, Etherson ML, Kennedy J, Fernandes AC, Marques CS, Hevner RF, Iwata T (2009) Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex. Neural Dev 4:4. doi:10.1186/1749-8104-4-4
Fukuchi-Shimogori T, Grove EA (2001) Neocortex patterning by the secreted signaling molecule FGF8. Science 294(5544):1071–1074
Garel S, Huffman KJ, Rubenstein JLR (2003) Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants. Development 130(9):1903–1914
Borello U, Cobos I, Long JE, McWhirter JR, Murre C, Rubenstein JL (2008) FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development. Neural Dev 3:17. doi:10.1186/1749-8104-3-17
Kobayashi D, Kobayashi M, Matsumoto K, Ogura T, Nakafuku M, Shimamura K (2002) Early subdivisions in the neural plate define distinct competence for inductive signals. Development 129(1):83–93
Vickaryous MK, Hall BK (2006) Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Biol Rev Camb Philos Soc: 1–31
Wells RB (2005) Cortical nneurons and circuits: a tutorial.
Subramanian L, Remedios R, Shetty A, Tole S (2009) Signals from the edges: the cortical hem and antihem in telencephalic development. Semin Cell Dev Biol 20(6):712–718. doi:10.1016/j.semcdb.2009.04.001
Machon O, Backman M, Machonova O, Kozmik Z, Vacik T, Andersen L, Krauss S (2007) A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev Biol 311(1):223–237. doi:10.1016/j.ydbio.2007.08.038
Assimacopoulos S, Grove EA, Ragsdale CW (2003) Identification of a Pax6-dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex. J Neurosci 23(16):6399–6403
Dou CL, Li S, Lai E (1999) Dual role of brain factor-1 in regulating growth and patterning of the cerebral hemispheres. Cereb Cortex 9(6):543–550
Muzio L, Mallamaci A (2005) Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the dorsomedial pallium. J Neurosci 25(17):4435–4441. doi:10.1523/jneurosci.4804-04.2005
Anderson SA, Marin O, Horn C, Jennings K, Rubenstein JL (2001) Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 128(3):353–363
Carney RS, Alfonso TB, Cohen D, Dai H, Nery S, Stoica B, Slotkin J, Bregman BS, Fishell G, Corbin JG (2006) Cell migration along the lateral cortical stream to the developing basal telencephalic limbic system. J Neurosci 26(45):11562–11574. doi:10.1523/jneurosci.3092-06.2006
Carney RS, Cocas LA, Hirata T, Mansfield K, Corbin JG (2009) Differential regulation of telencephalic pallial-subpallial boundary patterning by Pax6 and Gsh2. Cereb Cortex 19(4):745–759. doi:10.1093/cercor/bhn123
Maruoka Y, Ohbayashi N, Hoshikawa M, Itoh N, Hogan BL, Furuta Y (1998) Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo. Mech Dev 74(1–2):175–177
Xu J, Liu Z, Ornitz D (2000) Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures. Development 127(9):1833–1843
Nakamura H, Katahira T, Matsunaga E, Sato T (2005) Isthmus organizer for midbrain and hindbrain development. Brain Res Brain Res Rev 49(2):120–126
Meyers EN, Lewandoski M, Martin GR (1998) An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat Genet 18(2):136–141
Liu A, Losos K, Joyner AL (1999) FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development 126(21):4827–4838
Chi CL, Martinez S, Wurst W, Martin GR (2003) The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development 130(12):2633–2644
Saarimaki-Vire J, Peltopuro P, Lahti L, Naserke T, Blak AA, Vogt Weisenhorn DM, Yu K, Ornitz DM, Wurst W, Partanen J (2007) Fibroblast growth factor receptors cooperate to regulate neural progenitor properties in the developing midbrain and hindbrain. J Neurosci 27(32):8581–8592
Blaess S, Stephen D, Joyner AL (2008) Gli3 coordinates three-dimensional patterning and growth of the tectum and cerebellum by integrating Shh and Fgf8 signaling. Development 135(12):2093–2103. doi:10.1242/dev.015990
Yu T, Yaguchi Y, Echevarria D, Martinez S, Basson MA (2011) Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum. Development 138(14):2957–2968. doi:10.1242/dev.063784
Basson MA, Echevarria D, Ahn CP, Sudarov A, Joyner AL, Mason IJ, Martinez S, Martin GR (2008) Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development 135(5):889–898. doi:10.1242/dev.011569
Lin W, Jing N, Basson MA, Dierich A, Licht J, Ang SL (2005) Synergistic activity of Sef and Sprouty proteins in regulating the expression of Gbx2 in the mid-hindbrain region. Genesis 41(3):110–115. doi:10.1002/gene.20103
Crespo-Enriquez I, Partanen J, Martinez S, Echevarria D (2012) Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube. PLoS One 7(7):e39977. doi:10.1371/journal.pone.0039977
Eblaghie MC, Lunn JS, Dickinson RJ, Munsterberg AE, Sanz-Ezquerro JJ, Farrell ER, Mathers J, Keyse SM, Storey K, Tickle C (2003) Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick embryos. Curr Biol 13(12):1009–1018
Moses D, Teper Y, Gantois I, Finkelstein DI, Horne MK, Drago J (2006) Murine embryonic EGF-responsive ventral mesencephalic neurospheres display distinct regional specification and promote survival of dopaminergic neurons. Exp Neurol 199(1):209–221. doi:10.1016/j.expneurol.2006.02.120
Andrae J, Afink G, Zhang XQ, Wurst W, Nister M (2004) Forced expression of platelet-derived growth factor B in the mouse cerebellar primordium changes cell migration during midline fusion and causes cerebellar ectopia. Mol Cell Neurosci 26(2):308–321. doi:10.1016/j.mcn.2004.02.004
Bu J, Banki A, Wu Q, Nishiyama A (2004) Increased NG2+ glial cell proliferation and oligodendrocyte generation in the hypomyelinating mutant shiverer. Glia 48(1):51–63. doi:10.1002/glia.20055
Ligon KL, Fancy SP, Franklin RJ, Rowitch DH (2006) Olig gene function in CNS development and disease. Glia 54(1):1–10
Cai J, Qi Y, Hu X, Tan M, Liu Z, Zhang J, Li Q, Sander M, Qiu M (2005) Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45(1):41–53. doi:10.1016/j.neuron.2004.12.028
Kessaris N, Jamen F, Rubin LL, Richardson WD (2004) Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors. Development 131(6):1289–1298. doi:10.1242/dev.01027
Fogarty M, Richardson WD, Kessaris N (2005) A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord. Development 132(8):1951–1959. doi:10.1242/dev.01777
Chandran S, Kato H, Gerreli D, Compston A, Svendsen CN, Allen ND (2003) FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway. Development 130(26):6599–6609
Chandran S, Compston A, Jauniaux E, Gilson J, Blakemore W, Svendsen C (2004) Differential generation of oligodendrocytes from human and rodent embryonic spinal cord neural precursors. Glia 47(4):314–324
Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 9(2):173–179. doi:10.1038/nn1620
Rao RC, Boyd J, Padmanabhan R, Chenoweth JG, McKay RD (2009) Efficient serum-free derivation of oligodendrocyte precursors from neural stem cell-enriched cultures. Stem Cells 27(1):116–125. doi:10.1634/stemcells.2007-0205
Chojnacki A, Kelly JJ, Hader W, Weiss S (2008) Distinctions between fetal and adult human platelet-derived growth factor-responsive neural precursors. Ann Neurol 64(2):127–142
Tekki-Kessaris N, Woodruff R, Hall AC, Gaffield W, Kimura S, Stiles CD, Rowitch DH, Richardson WD (2001) Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Development 128(13):2545–2554
Mo Z, Zecevic N (2009) Human fetal radial glia cells generate oligodendrocytes in vitro. Glia 57(5):490–498. doi:10.1002/glia.20775
Naruse M, Nakahira E, Miyata T, Hitoshi S, Ikenaka K, Bansal R (2006) Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2. Dev Biol 297(1):262–273
Furusho M, Kaga Y, Ishii A, Hebert JM, Bansal R (2011) Fibroblast growth factor signaling is required for the generation of oligodendrocyte progenitors from the embryonic forebrain. J Neurosci 31(13):5055–5066. doi:10.1523/jneurosci.4800-10.2011
Hu BY, Du ZW, Li XJ, Ayala M, Zhang SC (2009) Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136(9):1443–1452
Chojnacki A, Weiss S (2004) Isolation of a novel platelet-derived growth factor-responsive precursor from the embryonic ventral forebrain. J Neurosci 24(48):10888–10899. doi:10.1523/jneurosci.3302-04.2004
Erlandsson A, Brannvall K, Gustafsdottir S, Westermark B, Forsberg-Nilsson K (2006) Autocrine/paracrine platelet-derived growth factor regulates proliferation of neural progenitor cells. Cancer Res 66(16):8042–8048
Erlandsson A, Enarsson M, Forsberg-Nilsson K (2001) Immature neurons from CNS stem cells proliferate in response to platelet-derived growth factor. J Neurosci 21(10):3483–3491
Hu JG, Fu SL, Wang YX, Li Y, Jiang XY, Wang XF, Qiu MS, Lu PH, Xu XM (2008) Platelet-derived growth factor-AA mediates oligodendrocyte lineage differentiation through activation of extracellular signal-regulated kinase signaling pathway. Neuroscience 151(1):138–147
McKinnon RD, Waldron S, Kiel ME (2005) PDGF a-receptor signal strength controls an RTK rheostat that integrates phosphoinositol 3'-kinase and phospholipase Cg pathways during oligodendrocyte maturation. J Neurosci 25(14):3499–3508
Woodruff RH, Fruttiger M, Richardson WD, Franklin RJ (2004) Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult CNS and their response following CNS demyelination. Mol Cell Neurosci 25(2):252–262. doi:10.1016/j.mcn.2003.10.014
Zeger M, Popken G, Zhang J, Xuan S, Lu QR, Schwab MH, Nave KA, Rowitch D, D’Ercole AJ, Ye P (2007) Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination. Glia 55(4):400–411. doi:10.1002/glia.20469
Bibollet-Bahena O, Almazan G (2009) IGF-1-stimulated protein synthesis in oligodendrocyte progenitors requires PI3K/mTOR/Akt and MEK/ERK pathways. J Neurochem 109(5):1440–1451
Annenkov A (2009) The insulin-like growth factor (IGF) receptor type 1 (IGF1R) as an essential component of the signalling network regulating neurogenesis. Mol Neurobiol 40(3):195–216
Ye P, Hu Q, Liu H, Yan Y, D’Ercole AJ (2010) b-catenin mediates insulin-like growth factor-I actions to promote cyclin D1 mRNA expression, cell proliferation and survival in oligodendroglial cultures. Glia 58(9):1031–1041. doi:10.1002/glia.20984
Murtie JC, Zhou YX, Le TQ, Vana AC, Armstrong RC (2005) PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination. Neurobiol Dis 19(1–2):171–182. doi:10.1016/j.nbd.2004.12.006
Baron W, Metz B, Bansal R, Hoekstra D, de Vries H (2000) PDGF and FGF-2 signaling in oligodendrocyte progenitor cells: regulation of proliferation and differentiation by multiple intracellular signaling pathways. Mol Cell Neurosci 15(3):314–329. doi:10.1006/mcne.1999.0827
Thommes KB, Hoppe J, Vetter H, Sachinidis A (1996) The synergistic effect of PDGF-AA and IGF-1 on VSMC proliferation might be explained by the differential activation of their intracellular signaling pathways. Exp Cell Res 226(1):59–66. doi:10.1006/excr.1996.0202
Pedraza CE, Monk R, Lei J, Hao Q, Macklin WB (2008) Production, characterization, and efficient transfection of highly pure oligodendrocyte precursor cultures from mouse embryonic neural progenitors. Glia 56(12):1339–1352. doi:10.1002/glia.20702
McKinnon RD, Matsui T, Dubois-Dalcq M, Aaronson SA (1990) FGF modulates the PDGF-driven pathway of oligodendrocyte development. Neuron 5(5):603–614
Watatani K, Hirabayashi Y, Itoh Y, Gotoh Y (2012) PDK1 regulates the generation of oligodendrocyte precursor cells at an early stage of mouse telencephalic development. Genes Cells 17(4):326–335. doi:10.1111/j.1365-2443.2012.01591.x
Ebner S, Dunbar M, McKinnon RD (2000) Distinct roles for PI3K in proliferation and survival of oligodendrocyte progenitor cells. J Neurosci Res 62(3):336–345
Frederick TJ, Wood TL (2004) IGF-I and FGF-2 coordinately enhance cyclin D1 and cyclin E-cdk2 association and activity to promote G1 progression in oligodendrocyte progenitor cells. Mol Cell Neurosci 25(3):480–492
Frederick TJ, Min J, Altieri SC, Mitchell NE, Wood TL (2007) Synergistic induction of cyclin D1 in oligodendrocyte progenitor cells by IGF-I and FGF-2 requires differential stimulation of multiple signaling pathways. Glia 55(10):1011–1022
Min J, Singh S, Fitzgerald-Bocarsly P, Wood TL (2012) Insulin-like growth factor I regulates G2/M progression through mammalian target of rapamycin signaling in oligodendrocyte progenitors. Glia 60(11):1684–1695. doi:10.1002/glia.22387
Chew LJ, Coley W, Cheng Y, Gallo V (2010) Mechanisms of regulation of oligodendrocyte development by p38 mitogen-activated protein kinase. J Neurosci 30(33):11011–11027. doi:10.1523/jneurosci.2546-10.2010
Kuo E, Park DK, Tzvetanova ID, Leiton CV, Cho BS, Colognato H (2010) Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in oligodendrocyte development. J Neurochem 113(1):200–212. doi:10.1111/j.1471-4159.2010.06596.x
Grossmann KS, Wende H, Paul FE, Cheret C, Garratt AN, Zurborg S, Feinberg K, Besser D, Schulz H, Peles E, Selbach M, Birchmeier W, Birchmeier C (2009) The tyrosine phosphatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development. Proc Natl Acad Sci U S A 106(39):16704–16709. doi:10.1073/pnas.0904336106
Zhu Y, Park J, Hu X, Zheng K, Li H, Cao Q, Feng GS, Qiu M (2010) Control of oligodendrocyte generation and proliferation by Shp2 protein tyrosine phosphatase. Glia 58(12):1407–1414. doi:10.1002/glia.21016
Yim SH, Hammer JA, Quarles RH (2001) Differences in signal transduction pathways by which platelet-derived and fibroblast growth factors activate extracellular signal-regulated kinase in differentiating oligodendrocytes. J Neurochem 76(6):1925–1934
Newbern JM, Li X, Shoemaker SE, Zhou J, Zhong J, Wu Y, Bonder D, Hollenback S, Coppola G, Geschwind DH, Landreth GE, Snider WD (2011) Specific functions for ERK/MAPK signaling during PNS development. Neuron 69(1):91–105. doi:10.1016/j.neuron.2010.12.003
Ishii A, Fyffe-Maricich SL, Furusho M, Miller RH, Bansal R (2012) ERK1/ERK2 MAPK signaling is required to increase myelin thickness independent of oligodendrocyte differentiation and initiation of myelination. J Neurosci 32(26):8855–8864. doi:10.1523/jneurosci.0137-12.2012
Guardiola-Diaz HM, Ishii A, Bansal R (2012) Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation. Glia 60(3):476–486. doi:10.1002/glia.22281
Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D, Weiss S, van der Kooy D (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13(5):1071–1082
Moe MC, Westerlund U, Varghese M, Berg-Johnsen J, Svensson M, Langmoen IA (2005) Development of neuronal networks from single stem cells harvested from the adult human brain. Neurosurgery 56(6):1182–1188, discussion 1188–1190
Zecevic N, Chen Y, Filipovic R (2005) Contributions of cortical subventricular zone to the development of the human cerebral cortex. J Comp Neurol 491(2):109–122. doi:10.1002/cne.20714
Walton NM, Sutter BM, Chen HX, Chang LJ, Roper SN, Scheffler B, Steindler DA (2006) Derivation and large-scale expansion of multipotent astroglial neural progenitors from adult human brain. Development 133(18):3671–3681
Lois C, Alvarez-Buylla A (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci U S A 90(5):2074–2077
Doetsch F (2003) A niche for adult neural stem cells. Curr Opin Genet Dev 13(5):543–550
Riquelme PA, Drapeau E, Doetsch F (2008) Brain micro-ecologies: neural stem cell niches in the adult mammalian brain. Philos Trans R Soc Lond B Biol Sci 363(1489):123–137. doi:10.1098/rstb.2006.2016
Platel JC, Gordon V, Heintz T, Bordey A (2009) GFAP-GFP neural progenitors are antigenically homogeneous and anchored in their enclosed mosaic niche. Glia 57(1):66–78. doi:10.1002/glia.20735
Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17(13):5046–5061
Liu X, Bolteus AJ, Balkin DM, Henschel O, Bordey A (2006) GFAP-expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54(5):394–410
Fricker-Gates RA (2006) Radial glia: a changing role in the central nervous system. Neuroreport 17(11):1081–1084
Bonfanti L, Peretto P (2007) Radial glial origin of the adult neural stem cells in the subventricular zone. Prog Neurobiol 83(1):24–36
Nyfeler Y, Kirch RD, Mantei N, Leone DP, Radtke F, Suter U, Taylor V (2005) Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal. EMBO J 24(19):3504–3515
Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28(3):713–726
Das AV, Mallya KB, Zhao X, Ahmad F, Bhattacharya S, Thoreson WB, Hegde GV, Ahmad I (2006) Neural stem cell properties of Muller glia in the mammalian retina: regulation by Notch and Wnt signaling. Dev Biol 299(1):283–302. doi:10.1016/j.ydbio.2006.07.029
Ramirez-Castillejo C, Sanchez-Sanchez F, Andreu-Agullo C, Ferron SR, Aroca-Aguilar JD, Sanchez P, Mira H, Escribano J, Farinas I (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9(3):331–339
Bauer S, Patterson PH (2006) Leukemia inhibitory factor promotes neural stem cell self-renewal in the adult brain. J Neurosci 26(46):12089–12099
Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442(7104):823–826
Machold R, Hayashi S, Rutlin M, Muzumdar MD, Nery S, Corbin JG, Gritli-Linde A, Dellovade T, Porter JA, Rubin LL, Dudek H, McMahon AP, Fishell G (2003) Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39(6):937–950
Garcion E, Faissner A, Ffrench-Constant C (2001) Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration. Development 128(13):2485–2496
Campos LS, Decker L, Taylor V, Skarnes W (2006) Notch, epidermal growth factor receptor, and b1-integrin pathways are coordinated in neural stem cells. J Biol Chem 281(8):5300–5309
Goldberg JS, Hirschi KK (2009) Diverse roles of the vasculature within the neural stem cell niche. Regen Med 4(6):879–897. doi:10.2217/rme.09.61
Milner R (2007) A novel three-dimensional system to study interactions between endothelial cells and neural cells of the developing central nervous system. BMC Neurosci 8(1):3
Chojnacki AK, Mak GK, Weiss S (2009) Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both? Nat Rev Neurosci 10(2):153–163
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255(5052):1707–1710
Doetsch F (2003) The glial identity of neural stem cells. Nat Neurosci 6(11):1127–1134. doi:10.1038/nn1144
Raponi E, Agenes F, Delphin C, Assard N, Baudier J, Legraverend C, Deloulme JC (2007) S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage. Glia 55(2):165–177. doi:10.1002/glia.20445
Morshead CM, van der Kooy D (1992) Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain. J Neurosci 12(1):249–256
Alexson TO, Hitoshi S, Coles BL, Bernstein A, van der Kooy D (2006) Notch signaling is required to maintain all neural stem cell populations—irrespective of spatial or temporal niche. Dev Neurosci 28(1–2):34–48
Fernando RN, Eleuteri B, Abdelhady S, Nussenzweig A, Andang M, Ernfors P (2011) Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells. Proc Natl Acad Sci U S A 108(14):5837–5842. doi:10.1073/pnas.1014993108
Suh Y, Obernier K, Holzl-Wenig G, Mandl C, Herrmann A, Worner K, Eckstein V, Ciccolini F (2009) Interaction between DLX2 and EGFR regulates proliferation and neurogenesis of SVZ precursors. Mol Cell Neurosci 42(4):308–314. doi:10.1016/j.mcn.2009.08.003
Lois C, Garcia-Verdugo JM, Alvarez-Buylla A (1996) Chain migration of neuronal precursors. Science 271(5251):978–981
Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137(4):433–457. doi:10.1002/cne.901370404
Tropepe V, Craig CG, Morshead CM, van der Kooy D (1997) Transforming growth factor-a null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci 17(20):7850–7859
Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17(15):5820–5829
Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM, Alvarez-Buylla A (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36(6):1021–1034
Fallon J, Reid S, Kinyamu R, Opole I, Opole R, Baratta J, Korc M, Endo TL, Duong A, Nguyen G, Karkehabadhi M, Twardzik D, Patel S, Loughlin S (2000) In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc Natl Acad Sci U S A 97(26):14686–14691. doi:10.1073/pnas.97.26.14686
Pastrana E, Cheng LC, Doetsch F (2009) Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci U S A 106(15):6387–6392
Cesetti T, Obernier K, Bengtson CP, Fila T, Mandl C, Holzl-Wenig G, Worner K, Eckstein V, Ciccolini F (2009) Analysis of stem cell lineage progression in the neonatal subventricular zone identifies EGFR+/NG2- cells as transit-amplifying precursors. Stem Cells 27(6):1443–1454
O’Keeffe GC, Tyers P, Aarsland D, Dalley JW, Barker RA, Caldwell MA (2009) Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF. Proc Natl Acad Sci U S A 106(21):8754–8759. doi:10.1073/pnas.0803955106
Aguirre A, Rubio ME, Gallo V (2010) Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature 467(7313):323–327. doi:10.1038/nature09347
Ferron SR, Pozo N, Laguna A, Aranda S, Porlan E, Moreno M, Fillat C, de la Luna S, Sanchez P, Arbones ML, Farinas I (2010) Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling. Cell Stem Cell 7(3):367–379. doi:10.1016/j.stem.2010.06.021
Chojnacki A, Mak G, Weiss S (2011) PDGFRa expression distinguishes GFAP-expressing neural stem cells from PDGF-responsive neural precursors in the adult periventricular area. J Neurosci 31(26):9503–9512. doi:10.1523/jneurosci.1531-11.2011
Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, Vandenberg S, Alvarez-Buylla A (2006) PDGFRa-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51(2):187–199
Xu G, Shen J, Ishii Y, Fukuchi M, Dang TC, Zheng Y, Hamashima T, Fujimori T, Tsuda M, Funa K, Sasahara M (2013) Functional analysis of platelet-derived growth factor receptor-beta in neural stem/progenitor cells. Neuroscience 238:195–208. doi:10.1016/j.neuroscience.2013.02.021
Ishii Y, Matsumoto Y, Watanabe R, Elmi M, Fujimori T, Nissen J, Cao Y, Nabeshima Y, Sasahara M, Funa K (2008) Characterization of neuroprogenitor cells expressing the PDGF b-receptor within the subventricular zone of postnatal mice. Mol Cell Neurosci 37(3):507–518. doi:10.1016/j.mcn.2007.11.006
Rivers LE, Young KM, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, Richardson WD (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 11(12):1392–1401. doi:10.1038/nn.2220
Menn B, Garcia-Verdugo JM, Yaschine C, Gonzalez-Perez O, Rowitch D, Alvarez-Buylla A (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26(30):7907–7918
Komitova M, Zhu X, Serwanski DR, Nishiyama A (2008) NG2 cells are distinct from neurogenic cells in the postnatal mouse subventricular zone. J Comp Neurol 512(5):702–716
Nishiyama A, Komitova M, Suzuki R, Zhu X (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10(1):9–22
Aguirre AA, Chittajallu R, Belachew S, Gallo V (2004) NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J Cell Biol 165(4):575–589. doi:10.1083/jcb.200311141
Aguirre A, Gallo V (2004) Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone. J Neurosci 24(46):10530–10541. doi:10.1523/jneurosci.3572-04.2004
Gonzalez-Perez O, Romero-Rodriguez R, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A (2009) Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem Cells 27(8):2032–2043. doi:10.1002/stem.119
Aguirre A, Dupree JL, Mangin JM, Gallo V (2007) A functional role for EGFR signaling in myelination and remyelination. Nat Neurosci 10(8):990–1002. doi:10.1038/nn1938
Ivkovic S, Canoll P, Goldman JE (2008) Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter. J Neurosci 28(4):914–922. doi:10.1523/jneurosci.4327-07.2008
Aguirre A, Rizvi TA, Ratner N, Gallo V (2005) Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors. J Neurosci 25(48):11092–11106. doi:10.1523/jneurosci.2981-05.2005
Gonzalez-Perez O, Quinones-Hinojosa A (2010) Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes. Glia 58(8):975–983. doi:10.1002/glia.20979
Lindberg OR, Brederlau A, Jansson A, Nannmark U, Cooper-Kuhn C, Kuhn HG (2012) Characterization of epidermal growth factor-induced dysplasia in the adult rat subventricular zone. Stem Cells Dev 21(8):1356–1366. doi:10.1089/scd.2011.0275
Danilov AI, Gomes-Leal W, Ahlenius H, Kokaia Z, Carlemalm E, Lindvall O (2009) Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone. Glia 57(2):136–152. doi:10.1002/glia.20741
Zheng W, Nowakowski RS, Vaccarino FM (2004) Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Dev Neurosci 26(2–4):181–196
Gomez-Pinilla F, Lee J, Cotman C (1992) Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection. J Neurosci 12(1):345–355
Bernal GM, Peterson DA (2011) Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells. Aging Cell 10(3):466–482. doi:10.1111/j.1474-9726.2011.00694.x
Chadashvili T, Peterson DA (2006) Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR-2) immunoreactivity in astrocytes of neurogenic and non-neurogenic regions of the young adult and aged rat brain. J Comp Neurol 498(1):1–15
Azim K, Raineteau O, Butt AM (2012) Intraventricular injection of FGF-2 promotes generation of oligodendrocyte-lineage cells in the postnatal and adult forebrain. Glia. doi:10.1002/glia.22413
Kalluri HS, Vemuganti R, Dempsey RJ (2007) Mechanism of insulin-like growth factor I-mediated proliferation of adult neural progenitor cells: role of Akt. Eur J Neurosci 25(4):1041–1048
Rafalski VA, Brunet A (2011) Energy metabolism in adult neural stem cell fate. Prog Neurobiol 93(2):182–203. doi:10.1016/j.pneurobio.2010.10.007
Yan YP, Sailor KA, Vemuganti R, Dempsey RJ (2006) Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation. Eur J Neurosci 24(1):45–54
Ma DK, Ponnusamy K, Song MR, Ming GL, Song H (2009) Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCg1 activation for self-renewal of adult neural stem cells. Mol Brain 2(1):16
Ponti G, Reitano E, Aimar P, Cattaneo E, Conti L, Bonfanti L (2010) Neural-specific inactivation of ShcA functions results in anatomical disorganization of subventricular zone neural stem cell niche in the adult brain. Neuroscience 168(1):314–322. doi:10.1016/j.neuroscience.2010.03.008
Ortensi B, Osti D, Pellegatta S, Pisati F, Brescia P, Fornasari L, Levi D, Gaetani P, Colombo P, Ferri A, Nicolis S, Finocchiaro G, Pelicci G (2012) Rai is a new regulator of neural progenitor migration and glioblastoma invasion. Stem Cells 30(5):817–832. doi:10.1002/stem.1056
Navarro-Quiroga I, Hernandez-Valdes M, Lin SL, Naegele JR (2006) Postnatal cellular contributions of the hippocampus subventricular zone to the dentate gyrus, corpus callosum, fimbria, and cerebral cortex. J Comp Neurol 497(5):833–845
Ponti G, Peretto P, Bonfanti L (2006) A subpial, transitory germinal zone forms chains of neuronal precursors in the rabbit cerebellum. Dev Biol 294(1):168–180
Sottile V, Li M, Scotting PJ (2006) Stem cell marker expression in the Bergmann glia population of the adult mouse brain. Brain Res 1099(1):8–17
Pekcec A, Loscher W, Potschka H (2006) Neurogenesis in the adult rat piriform cortex. Neuroreport 17(6):571–574
Moyse E, Bauer S, Charrier C, Coronas V, Krantic S, Jean A (2006) Neurogenesis and neural stem cells in the dorsal vagal complex of adult rat brain: new vistas about autonomic regulations—a review. Auton Neurosci 126–127:50–58. doi:10.1016/j.autneu.2006.03.006
Pecchi E, Dallaporta M, Charrier C, Pio J, Jean A, Moyse E, Troadec JD (2007) Glial fibrillary acidic protein (GFAP)-positive radial-like cells are present in the vicinity of proliferative progenitors in the nucleus tractus solitarius of adult rat. J Comp Neurol 501(3):353–368
Ahmed AI, Shtaya AB, Zaben MJ, Owens EV, Kiecker C, Gray WP (2012) Endogenous GFAP-positive neural stem/progenitor cells in the postnatal mouse cortex are activated following traumatic brain injury. J Neurotrauma 29(5):828–842. doi:10.1089/neu.2011.1923
Stevens HE, Jiang GY, Schwartz ML, Vaccarino FM (2012) Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus. Biol Psychiatry 71(12):1090–1098. doi:10.1016/j.biopsych.2012.03.013
Weickert CS, Kittell DA, Saunders RC, Herman MM, Horlick RA, Kleinman JE, Hyde TM (2005) Basic fibroblast growth factor and fibroblast growth factor receptor-1 in the human hippocampal formation. Neuroscience 131(1):219–233. doi:10.1016/j.neuroscience.2004.09.070
Trejo JL, Llorens-Martin MV, Torres-Aleman I (2008) The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci 37(2):402–411
Glasper ER, Llorens-Martin MV, Leuner B, Gould E, Trejo JL (2010) Blockade of insulin-like growth factor-I has complex effects on structural plasticity in the hippocampus. Hippocampus 20(6):706–712. doi:10.1002/hipo.20672
Llorens-Martin M, Torres-Aleman I, Trejo JL (2009) Mechanisms mediating brain plasticity: IGF1 and adult hippocampal neurogenesis. Neuroscientist 15(2):134–148
Zou J, Pan YW, Wang Z, Chang SY, Wang W, Wang X, Tournier C, Storm DR, Xia Z (2012) Targeted deletion of ERK5 MAP kinase in the developing nervous system impairs development of GABAergic interneurons in the main olfactory bulb and behavioral discrimination between structurally similar odorants. J Neurosci 32(12):4118–4132. doi:10.1523/jneurosci.6260-11.2012
Pan YW, Chan GC, Kuo CT, Storm DR, Xia Z (2012) Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory. J Neurosci 32(19):6444–6455. doi:10.1523/jneurosci.6076-11.2012
Polito A, Reynolds R (2005) NG2-expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system. J Anat 207(6):707–716. doi:10.1111/j.1469-7580.2005.00454.x
Dawson MR, Polito A, Levine JM, Reynolds R (2003) NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci 24(2):476–488
Calver AR, Hall AC, Yu WP, Walsh FS, Heath JK, Betsholtz C, Richardson WD (1998) Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron 20(5):869–882
Nazarenko I, Hedren A, Sjodin H, Orrego A, Andrae J, Afink GB, Nister M, Lindstrom MS (2011) Brain abnormalities and glioma-like lesions in mice overexpressing the long isoform of PDGF-A in astrocytic cells. PLoS One 6(4):e18303. doi:10.1371/journal.pone.0018303
Mason JL, Goldman JE (2002) A2B5+ and O4+ Cycling progenitors in the adult forebrain white matter respond differentially to PDGF-AA, FGF-2, and IGF-1. Mol Cell Neurosci 20(1):30–42
Cohen RI, Chandross KJ (2000) Fibroblast growth factor-9 modulates the expression of myelin related proteins and multiple fibroblast growth factor receptors in developing oligodendrocytes. J Neurosci Res 61(3):273–287
Fortin D, Rom E, Sun H, Yayon A, Bansal R (2005) Distinct fibroblast growth factor (FGF)/FGF receptor signaling pairs initiate diverse cellular responses in the oligodendrocyte lineage. J Neurosci 25(32):7470–7479
Bansal R, Lakhina V, Remedios R, Tole S (2003) Expression of FGF receptors 1, 2, 3 in the embryonic and postnatal mouse brain compared with PDGFRa, Olig2 and Plp/dm20: implications for oligodendrocyte development. Dev Neurosci 25(2–4):83–95
Oh LY, Denninger A, Colvin JS, Vyas A, Tole S, Ornitz DM, Bansal R (2003) Fibroblast growth factor receptor 3 signaling regulates the onset of oligodendrocyte terminal differentiation. J Neurosci 23(3):883–894
Bryant MR, Marta CB, Kim FS, Bansal R (2009) Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes. Glia 57(9):935–946. doi:10.1002/glia.20818
Zhou YX, Flint NC, Murtie JC, Le TQ, Armstrong RC (2006) Retroviral lineage analysis of fibroblast growth factor receptor signaling in FGF2 inhibition of oligodendrocyte progenitor differentiation. Glia 54(6):578–590. doi:10.1002/glia.20410
Armstrong RC, Le TQ, Flint NC, Vana AC, Zhou YX (2006) Endogenous cell repair of chronic demyelination. J Neuropathol Exp Neurol 65(3):245–256. doi:10.1097/01.jnen.0000205142.08716.7e
Zhou YX, Pannu R, Le TQ, Armstrong RC (2012) Fibroblast growth factor 1 (FGFR1) modulation regulates repair capacity of oligodendrocyte progenitor cells following chronic demyelination. Neurobiol Dis 45(1):196–205. doi:10.1016/j.nbd.2011.08.004
Zhou YX, Armstrong RC (2007) Interaction of fibroblast growth factor 2 (FGF2) and notch signaling components in inhibition of oligodendrocyte progenitor (OP) differentiation. Neurosci Lett 421(1):27–32. doi:10.1016/j.neulet.2007.05.020
Furusho M, Dupree JL, Nave KA, Bansal R (2012) Fibroblast growth factor receptor signaling in oligodendrocytes regulates myelin sheath thickness. J Neurosci 32(19):6631–6641. doi:10.1523/jneurosci.6005-11.2012
Boockvar JA, Kapitonov D, Kapoor G, Schouten J, Counelis GJ, Bogler O, Snyder EY, McIntosh TK, O’Rourke DM (2003) Constitutive EGFR signaling confers a motile phenotype to neural stem cells. Mol Cell Neurosci 24(4):1116–1130
Ju P, Zhang S, Yeap Y, Feng Z (2012) Induction of neuronal phenotypes from NG2+ glial progenitors by inhibiting epidermal growth factor receptor in mouse spinal cord injury. Glia 60(11):1801–1814. doi:10.1002/glia.22398
White RE, Rao M, Gensel JC, McTigue DM, Kaspar BK, Jakeman LB (2011) Transforming growth factor alpha transforms astrocytes to a growth-supportive phenotype after spinal cord injury. J Neurosci 31(42):15173–15187. doi:10.1523/jneurosci.3441-11.2011
Ebert AD, Beres AJ, Barber AE, Svendsen CN (2008) Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson’s disease. Exp Neurol 209(1):213–223. doi:10.1016/j.expneurol.2007.09.022
Miltiadous P, Kouroupi G, Stamatakis A, Koutsoudaki PN, Matsas R, Stylianopoulou F (2013) Subventricular zone-derived neural stem cell grafts protect against hippocampal degeneration and restore cognitive function in the mouse following intrahippocampal kainic acid administration. Stem Cells Transl Med 2(3):185–198. doi:10.5966/sctm.2012-0074
Dayer AG, Jenny B, Sauvain MO, Potter G, Salmon P, Zgraggen E, Kanemitsu M, Gascon E, Sizonenko S, Trono D, Kiss JZ (2007) Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex. Brain 130(Pt 11):2962–2976
Jenny B, Kanemitsu M, Tsupykov O, Potter G, Salmon P, Zgraggen E, Gascon E, Skibo G, Dayer AG, Kiss JZ (2009) Fibroblast growth factor-2 0overexpression in transplanted neural progenitors promotes perivascular cluster formation with a neurogenic potential. Stem Cells 27(6):1309–1317
Ouchi Y, Banno Y, Shimizu Y, Ando S, Hasegawa H, Adachi K, Iwamoto T (2013) Reduced adult hippocampal neurogenesis and working memory deficits in the Dgcr8-deficient mouse model of 22q11.2 deletion-associated schizophrenia can be rescued by IGF2. J Neurosci 33(22):9408–9419. doi:10.1523/jneurosci.2700-12.2013
Nakaguchi K, Jinnou H, Kaneko N, Sawada M, Hikita T, Saitoh S, Tabata Y, Sawamoto K (2012) Growth factors released from gelatin hydrogel microspheres increase new neurons in the adult mouse brain. Stem Cells Int 2012:915160. doi:10.1155/2012/915160
Zhu W, Fan Y, Hao Q, Shen F, Hashimoto T, Yang GY, Gasmi M, Bartus RT, Young WL, Chen Y (2009) Postischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke. J Cereb Blood Flow Metab 29(9):1528–1537. doi:10.1038/jcbfm.2009.75
Oya S, Yoshikawa G, Takai K, Tanaka J, Higashiyama S, Saito N, Kirino T, Kawahara N (2008) Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia. Neuroreport 19(8):805–809. doi:10.1097/WNR.0b013e3282ff8641
Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C, Bakowska JC, Breakefield XO, Moskowitz MA (2001) FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci U S A 98(10):5874–5879. doi:10.1073/pnas.101034998
Sun D, Bullock MR, McGinn MJ, Zhou Z, Altememi N, Hagood S, Hamm R, Colello RJ (2009) Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury. Exp Neurol 216(1):56–65. doi:10.1016/j.expneurol.2008.11.011
Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A, Greenberg DA (2003) Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2(3):175–183
Ayuso-Sacido A, Graham C, Greenfield JP, Boockvar JA (2006) The duality of epidermal growth factor receptor (EGFR) signaling and neural stem cell phenotype: cell enhancer or cell transformer? Curr Stem Cell Res Ther 1(3):387–394
Alzheimer C, Werner S (2002) Fibroblast growth factors and neuroprotection. Adv Exp Med Biol 513:335–351
O’Connor R, Kauffmann-Zeh A, Liu Y, Lehar S, Evan GI, Baserga R, Blattler WA (1997) Identification of domains of the insulin-like growth factor I receptor that are required for protection from apoptosis. Mol Cell Biol 17(1):427–435
Acknowledgments
The author was supported by funding from the National Multiple Sclerosis Society of the USA.
Conflict of interest
The author declares that he has no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Annenkov, A. Receptor Tyrosine Kinase (RTK) Signalling in the Control of Neural Stem and Progenitor Cell (NSPC) Development. Mol Neurobiol 49, 440–471 (2014). https://doi.org/10.1007/s12035-013-8532-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-013-8532-5