Skip to main content

Proneural Genes and Cerebellar Neurogenesis in the Ventricular Zone and Upper Rhombic Lip

  • Reference work entry
Handbook of the Cerebellum and Cerebellar Disorders

Abstract

The cerebellar primordium arises between embryonic days 8.5 and 9.5 from dorsal rhombomere 1, adjacent to the fourth ventricle. Cerebellar patterning requires the concerted action of morphogens secreted by the rhombic lip and roof plate, and leads to the formation of two main neurogenetic centers, the upper rhombic lip and ventricular zone, from which glutamatergic and GABAergic neurons arise, respectively. These territories contain gene expression microdomains that are partially overlapping and, among others, express proneural genes. This gene family is tightly conserved in evolution and encodes basic helix-loop-helix transcription factors implicated in many neurogenetic events, ranging from cell-fate specification to terminal differentiation of a variety of neuronal types across the embryonic nervous system. The present paper deals with the established or suggested roles of proneural genes in cerebellar neurogenesis. Of the proneural genes examined in this chapter, Atoh1 plays a quintessential role in the specification and development of granule cells and other cerebellar glutamatergic neurons. Besides playing key roles at early stages in these early developmental events, Atoh1 is a key player in the clonal expansion of GC progenitors of the external granule layer. NeuroD, formerly regarded as a proneural gene, acts as a master gene in granule cell differentiation, survival, and dendrite formation. Ascl1 participates in GABA interneuron and cerebellar nuclei neurons generation, and suppresses astrogliogenesis. Conversely, little is known to date about the role(s) of Neurog1 and Neurog2 in cerebellar neurogenesis, and a combination of loss- and gain-of-function studies is required to elucidate their role, if any, in cerebellar neurogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Similar content being viewed by others

References

  • Abraham H, Tornoczky T, Kosztolanyi G, Seress L (2001) Cell formation in the cortical layers of the developing human cerebellum. Int J Dev Neurosci 19:53–62

    Article  PubMed  CAS  Google Scholar 

  • Akazawa C, Ishibashi M, Shimizu C, Nakanishi S, Kageyama R (1995) A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system. J Biol Chem 270:8730–8738

    Article  PubMed  CAS  Google Scholar 

  • Alder J, Lee KJ, Jessell TM, Hatten ME (1999) Generation of cerebellar granule neurons in vivo by transplantation of BMP-treated neural progenitor cells. Nat Neurosci 2:535–540

    Article  PubMed  CAS  Google Scholar 

  • Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776

    Article  PubMed  CAS  Google Scholar 

  • Battiste J, Helms AW, Kim EJ, Savage TK, Lagace DC, Mandyam CD, Eisch AJ, Miyoshi G, Johnson JE (2007) Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord. Development 134:285–293

    Article  PubMed  CAS  Google Scholar 

  • Ben-Arie N, Bellen HJ, Armstrong DL, McCall AE, Gordadze PR, Guo Q, Matzuk MM, Zoghbi HY (1997) Math1 is essential for genesis of cerebellar granule neurons. Nature 390:169–172

    Article  PubMed  CAS  Google Scholar 

  • Ben-Arie N, Hassan BA, Bermingham NA, Malicki DM, Armstrong D, Matzuk M, Bellen HJ, Zoghbi HY (2000) Functional conservation of atonal and Math1 in the CNS and PNS. Development 127:1039–1048

    PubMed  CAS  Google Scholar 

  • Bermingham NA, Hassan BA, Wang VY, Fernandez M, Banfi S, Bellen HJ, Fritzsch B, Zoghbi HY (2001) Proprioceptor pathway development is dependent on Math1. Neuron 30:411–422

    Article  PubMed  CAS  Google Scholar 

  • Blader P, Fischer N, Gradwohl G, Guillemot F, Strahle U (1997) The activity of neurogenin1 is controlled by local cues in the zebrafish embryo. Development 124:4557–4569

    PubMed  CAS  Google Scholar 

  • Cajal S (1889) Sobre las fibras nerviosas de la capa granulosa del cerebelo. Revista Trimestral de Histolog a Normal y Patológica 3–4:107–118

    Google Scholar 

  • Campuzano S, Modolell J (1992) Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet 8:202–208

    PubMed  CAS  Google Scholar 

  • Casarosa S, Fode C, Guillemot F (1999) Mash1 regulates neurogenesis in the ventral telencephalon. Development 126:525–534

    PubMed  CAS  Google Scholar 

  • Cau E, Gradwohl G, Fode C, Guillemot F (1997) Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Development 124:1611–1621

    PubMed  CAS  Google Scholar 

  • Chen P, Johnson JE, Zoghbi HY, Segil N (2002) The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. Development 129:2495–2505

    Article  PubMed  CAS  Google Scholar 

  • Chien CT (1996) Neuronal type information encoded in the basic-helix-loop-helix domain of proneural genes. Proc Natl Acad Sci USA 93:13239–13244

    Article  PubMed  CAS  Google Scholar 

  • Chizhikov VV, Millen KJ (2004) Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. J Neurosci 24:5694–5703

    Article  PubMed  CAS  Google Scholar 

  • Chizhikov VV, Lindgren AG, Currle DS, Rose MF, Monuki ES, Millen KJ (2006) The roof plate regulates cerebellar cell-type specification and proliferation. Development 133:2793–2804

    Article  PubMed  CAS  Google Scholar 

  • Crossley PH, Martinez S, Martin GR (1996) Midbrain development induced by FGF8 in the chick embryo. Nature 380:66–68

    Article  PubMed  CAS  Google Scholar 

  • Dahmane N, Ruiz-i-Altaba A (1999) Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126:3089–3100

    PubMed  Google Scholar 

  • Dalgard CL, Zhou Q, Lundell TG, Doughty ML (2011) Altered gene expression in the emerging cerebellar primordium of Neurog1 −/− mice. Brain Res 1388:12–21

    Article  PubMed  CAS  Google Scholar 

  • Eberhart CG, Tihan T, Burger PC (2000) Nuclear localization and mutation of beta-catenin in medulloblastomas. J Neuropathol Exp Neurol 59:333–337

    PubMed  CAS  Google Scholar 

  • Ebert PJ, Timmer JR, Nakada Y, Helms AW, Parab PB, Liu Y, Hunsaker TL, Johnson JE (2003) Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation. Development 130:1949–1959

    Article  PubMed  CAS  Google Scholar 

  • Englund C, Kowalczyk T, Daza RA, Dagan A, Lau C, Rose MF, Hevner RF (2006) Unipolar brush cells of the cerebellum are produced in the rhombic lip and migrate through developing white matter. J Neurosci 26:9184–9195

    Article  PubMed  CAS  Google Scholar 

  • Flora A, Klisch TJ, Schuster G, Zoghbi HY (2009) Deletion of Atoh1 Disrupts Sonic Hedgehog Signaling in the Developing Cerebellum and Prevents Medulloblastoma. Science 326:1424–1427

    Article  PubMed  CAS  Google Scholar 

  • Fode C, Gradwohl G, Morin X, Dierich A, LeMeur M, Goridis C, Guillemot F (1998) The bHLH protein NEUROGENIN 2 is a determination factor for epibranchial placode-derived sensory neurons. Neuron 20:483–494

    Article  PubMed  CAS  Google Scholar 

  • Fode C, Ma Q, Casarosa S, Ang SL, Anderson DJ, Guillemot F (2000) A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev 14:67–80

    PubMed  CAS  Google Scholar 

  • Gaudilliere B, Konishi Y, de la Iglesia N, Yao G, Bonni A (2004) A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis. Neuron 41:229–241

    Article  PubMed  CAS  Google Scholar 

  • Gazit R, Krizhanovsky V, Ben-Arie N (2004) Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway. Development 131:903–913

    Article  PubMed  CAS  Google Scholar 

  • Ghysen A, Dambly-Chaudiere C (1988) From DNA to form: the achaete-scute complex. Genes Dev 2:495–501

    Article  PubMed  CAS  Google Scholar 

  • Goridis C, Brunet JF (1999) Transcriptional control of neurotransmitter phenotype. Curr Opin Neurobiol 9:47–53

    Article  PubMed  CAS  Google Scholar 

  • Goulding SE, zur Lage P, Jarman AP (2000) amos, a proneural gene for Drosophila olfactory sense organs that is regulated by lozenge. Neuron 25:69–78

    Article  PubMed  CAS  Google Scholar 

  • Gowan K, Helms AW, Hunsaker TL, Collisson T, Ebert PJ, Odom R, Johnson JE (2001) Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons. Neuron 31:219–232

    Article  PubMed  CAS  Google Scholar 

  • Grimaldi P, Parras C, Guillemot F, Rossi F, Wassef M (2009) Origins and control of the differentiation of inhibitory interneurons and glia in the cerebellum. Dev Biol 328:422–433

    Article  PubMed  CAS  Google Scholar 

  • Harris J, Moreno S, Shaw G, Mugnaini E (1993) Unusual neurofilament composition in cerebellar unipolar brush neurons. J Neurocytol 22:1039–1059

    Article  PubMed  CAS  Google Scholar 

  • Hatten ME, Heintz N (1995) Mechanisms of neural patterning and specification in the developing cerebellum. Ann Rev Neurosci 18:385–408

    Article  PubMed  CAS  Google Scholar 

  • Helms AW, Gowan K, Abney A, Savage T, Johnson JE (2001) Overexpression of MATH1 disrupts the coordination of neural differentiation in cerebellum development. Mol Cell Neurosci 17:671–682

    Article  PubMed  CAS  Google Scholar 

  • Helms AW, Battiste J, Henke RM, Nakada Y, Simplicio N, Guillemot F, Johnson JE (2005) Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons. Development 132:2709–2719

    Article  PubMed  CAS  Google Scholar 

  • Herrup K, Kuemerle B (1997) The compartmentalization of the cerebellum [Review]. Annu Rev Neurosci 20:61–90

    Article  PubMed  CAS  Google Scholar 

  • Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, Fukuda A, Fuse T, Matsuo N, Sone M, Watanabe M, Bito H, Terashima T, Wright CV, Kawaguchi Y, Nakao K, Nabeshima Y (2005) Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47:201–213

    Article  PubMed  CAS  Google Scholar 

  • Jan Y, Jan L (1994) Neuronal cell fate specification in Drosophila. Curr Opin Neurobiol 4:8–13

    Article  PubMed  CAS  Google Scholar 

  • Jensen P, Smeyne R, Goldowitz D (2004) Analysis of cerebellar development in math1 null embryos and chimeras. J Neurosci 24:2202–2211

    Article  PubMed  CAS  Google Scholar 

  • Joyner AL, Zervas M (2006) Genetic inducible fate mapping in mouse: establishing genetic lineages and defining genetic neuroanatomy in the nervous system. Dev Dyn 235:2376–2385

    Article  PubMed  Google Scholar 

  • Kanekar S, Perron M, Dorsky R, Harris WA, Jan LY, Jan YN, Vetter ML (1997) Xath5 participates in a network of bHLH genes in the developing Xenopus retina. Neuron 19:981–994

    Article  PubMed  CAS  Google Scholar 

  • Kim P (1997) XATH-1, a vertebrate homolog of Drosophila atonal, induces a neuronal differentiation within ectodermal progenitors. Dev Biol 187:1–12

    Article  PubMed  CAS  Google Scholar 

  • Kim EJ, Battiste J, Nakagawa Y, Johnson JE (2008) Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture. Mol Cell Neurosci 38:595–606

    Article  PubMed  CAS  Google Scholar 

  • Kim EJ, Hori K, Wyckoff A, Dickel LK, Koundakjian EJ, Goodrich LV, Johnson JE (2011) Spatiotemporal fate map of neurogenin1 (Neurog1) lineages in the mouse central nervous system. J Comp Neurol 519:1355–1370

    Article  PubMed  CAS  Google Scholar 

  • Ledent V, Vervoort M (2001) The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis. Genome Res 11:754–770

    Article  PubMed  CAS  Google Scholar 

  • Lee JE (1997) Basic helix-loop-helix genes in neural development. Curr Opin Neurobiol 7:13–20

    Article  PubMed  Google Scholar 

  • Lee J, Hollenberg S, Snider L, Turner D, Lipnick N, Weintraub H (1995) Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Science 268:836–844

    Article  PubMed  CAS  Google Scholar 

  • Lee JK, Cho JH, Hwang WS, Lee YD, Reu DS, Suh-Kim H (2000) Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system. Dev Dyn 217:361–367

    Article  PubMed  CAS  Google Scholar 

  • Lewis PM, Gritli-Linde A, Smeyne R, Kottmann A, McMahon AP (2004) Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol 270:393–410

    Article  PubMed  CAS  Google Scholar 

  • Liu A, Joyner AL (2001) Early anterior/posterior patterning of the midbrain and cerebellum. Annu Rev Neurosci 24:869–896

    Article  PubMed  CAS  Google Scholar 

  • Lundell TG, Zhou Q, Doughty ML (2009) Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice. Dev Dyn 238:3310–3325

    Article  PubMed  CAS  Google Scholar 

  • Ma Q, Kintner C, Anderson DJ (1996) Identification of neurogenin, a vertebrate neuronal determination gene. Cell 87:43–52

    Article  PubMed  CAS  Google Scholar 

  • Ma Q, Chen Z, del Barco BI, de la Pompa JL, Anderson DJ (1998) neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron 20:469–482

    Article  PubMed  CAS  Google Scholar 

  • Ma Q, Fode C, Guillemot F, Anderson DJ (1999) Neurogenin1 and neurogenin2 control two distinct waves of neurogenesis in developing dorsal root ganglia. Genes Dev 13:1717–1728

    Article  PubMed  CAS  Google Scholar 

  • Machold R, Fishell G (2005) Math1 is expressed in temporally discrete pools of cerebellar rhombic-lip neural progenitors. Neuron 48:17–24

    Article  PubMed  CAS  Google Scholar 

  • Marin F, Puelles L (1994) Patterning of the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus. Dev Biol 163:19–37

    Article  PubMed  CAS  Google Scholar 

  • Marin F, Puelles L (1995) Morphological fate of rhombomeres in quail/chick chimeras: a segmental analysis of hindbrain nuclei. Eur J Neurosci 7:1714–1738

    Article  PubMed  CAS  Google Scholar 

  • Martinez S, Alvarado-Mallart RM (1987) Rostral cerebellum originates from the caudal portion of the so-called mesencephalic vesicle: a study using quail/chick chimeras. Eur J Neurosci 1:549–560

    Article  Google Scholar 

  • Martinez S, Crossley PH, Cobos I, Rubenstein JL, Martin GR (1999) FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Development 126:1189–1200

    PubMed  CAS  Google Scholar 

  • Miyata T, Maeda T, Lee JE (1999) NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes Dev 13:1647–1652

    Article  PubMed  CAS  Google Scholar 

  • Mugnaini E, Floris A (1994) The unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex. J Comp Neurol 339:174–180

    Article  PubMed  CAS  Google Scholar 

  • Novak A, Guo C, Yang W, Nagy A, Lobe CG (2000) Genesis 28(3–4):147–155

    Article  PubMed  CAS  Google Scholar 

  • Nunzi MG, Birnstiel S, Bhattacharyya BJ, Slater NT, Mugnaini E (2001) Unipolar brush cells form a glutamatergic projection system within the mouse cerebellar cortex. J Comp Neurol 434:329–341

    Article  PubMed  CAS  Google Scholar 

  • Olson EC, Schinder AF, Dantzker JL, Marcus EA, Spitzer NC, Harris WA (1998) Properties of ectopic neurons induced by Xenopus neurogenin1 misexpression. Mol Cell Neurosci 12:281–299

    Article  PubMed  CAS  Google Scholar 

  • Parras C (1996) Control of neural precursor specification by proneural proteins in the CNS of Drosophila. EMBO J 15:6394–6399

    PubMed  CAS  Google Scholar 

  • Pascual M, Abasolo I, Mingorance-Le Meur A, Martinez A, Del Rio JA, Wright CV, Real FX, Soriano E (2007) Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Proc Natl Acad Sci USA 104:5193–5198

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G (1995) The rat nervous system. Academic, San Diego

    Google Scholar 

  • Perez SE, Rebelo S, Anderson DJ (1999) Early specification of sensory neuron fate revealed by expression and function of neurogenins in the chick embryo. Development 126:1715–1728

    PubMed  CAS  Google Scholar 

  • Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez I (1990) Competence to develop sensory organs is temporally and spatially regulated in Drosophila epidermal primordia. EMBO J 9:3583–3592

    PubMed  CAS  Google Scholar 

  • Salsano E, Pollo B, Eoli M, Giordana MT, Finocchiaro G (2004) Expression of MATH1, a marker of cerebellar granule cell progenitors, identifies different medulloblastoma sub-types. Neurosci Lett 370:180–185

    Article  PubMed  CAS  Google Scholar 

  • Salsano E, Croci L, Maderna E, Lupo L, Pollo B, Giordana MT, Consalez G, Finocchiaro G (2007) Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1 identifies a subgroup of medulloblastomas not expressing ATOH1. Neuro Oncol 9:298–307

    Article  PubMed  CAS  Google Scholar 

  • Schaper A (1897) Die frühsten differenzierungsvorgänge im centralnervensystem. Arch Entw Mech Org 5:81–132

    Google Scholar 

  • Schmahmann JD (2004) Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 16:367–378

    Article  PubMed  Google Scholar 

  • Schuurmans C, Armant O, Nieto M, Stenman JM, Britz O, Klenin N, Brown C, Langevin LM, Seibt J, Tang H, Cunningham JM, Dyck R, Walsh C, Campbell K, Polleux F, Guillemot F (2004) Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways. EMBO J 23:2892–2902

    Article  PubMed  CAS  Google Scholar 

  • Simionato E, Ledent V, Richards G, Thomas-Chollier M, Kerner P, Coornaert D, Degnan BM, Vervoort M (2007) Origin and diversification of the basic helix-loop-helix gene family in metazoans: insights from comparative genomics. BMC Evol Biol 7:33

    Article  PubMed  Google Scholar 

  • Skeath JB, Doe CQ (1996) The achaete-scute complex proneural genes contribute to neural precursor specification in the Drosophila CNS. Curr Biol 6:1146–1152

    Article  PubMed  CAS  Google Scholar 

  • Smeyne RJ, Chu T, Lewin A, Bian F, SC S, Kunsch C, Lira SA, Oberdick J (1995) Local control of granule cell generation by cerebellar Purkinje cells. Mol Cell Neurosci 6:230–251

    Article  PubMed  CAS  Google Scholar 

  • Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21:70–71

    Article  PubMed  CAS  Google Scholar 

  • Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell TM, Costantini F (2001) Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 1:4

    Article  PubMed  CAS  Google Scholar 

  • Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, Chintagumpala M, Adesina A, Ashley DM, Kellie SJ, Taylor MD, Curran T, Gajjar A, Gilbertson RJ (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924–1931

    Article  PubMed  CAS  Google Scholar 

  • Villavicencio EH, Walterhouse DO, Iannaccone PM (2000) The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet 67:1047–1054

    PubMed  CAS  Google Scholar 

  • Vue TY, Aaker J, Taniguchi A, Kazemzadeh C, Skidmore JM, Martin DM, Martin JF, Treier M, Nakagawa Y (2007) Characterization of progenitor domains in the developing mouse thalamus. J Comp Neurol 505:73–91

    Article  PubMed  CAS  Google Scholar 

  • Wallace VA (1999) Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum. Curr Biol 9:445–448

    Article  PubMed  CAS  Google Scholar 

  • Wang SW (2001) Requirement for math5 in the development of retinal ganglion cells. Genes Dev 15:24–29

    Article  PubMed  CAS  Google Scholar 

  • Wang VY, Rose MF, Zoghbi HY (2005) Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum. Neuron 48:31–43

    Article  PubMed  CAS  Google Scholar 

  • Wassarman KM, Lewandoski M, Campbell K, Joyner AL, Rubenstein JL, Martinez S, Martin GR (1997) Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development 124:2923–2934

    PubMed  CAS  Google Scholar 

  • Wechsler-Reya RJ, Scott MP (1999) Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22:103–114

    Article  PubMed  CAS  Google Scholar 

  • Yun K, Fischman S, Johnson J, Hrabe de Angelis M, Weinmaster G, Rubenstein JL (2002) Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon. Development 129:5029–5040

    PubMed  CAS  Google Scholar 

  • Zhao Y, Kwan K-M, Mailloux C, Lee W-K, Grinberg A, Wurst W, Behringer R, Westphal H (2007) LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactors Ldb1, control Purkinje cell differentiation in the developing cerebellum. Proc Natl Acad Sci USA 104:13182–13186

    Article  PubMed  CAS  Google Scholar 

  • Zhao H, Ayrault O, Zindy F, Kim JH, Roussel MF (2008) Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development. Genes Dev 22:722–727

    Article  PubMed  CAS  Google Scholar 

  • Zordan P, Croci L, Hawkes R, Consalez GG (2008) Comparative analysis of proneural gene expression in the embryonic cerebellum. Dev Dyn 237:1726–1735

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Giacomo Consalez’ research has been supported by grants from Ataxia UK, Compagnia di San Paolo, the EU (EuroSyStem), and the Berlucchi Foundation. Further support has come from the Stayton family in honor of Dr. Chester A. Stayton of Indianapolis, Indiana, USA. This review is dedicated to his cherished memory.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G. Giacomo Consalez .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Consalez, G.G., Florio, M., Massimino, L., Croci, L. (2013). Proneural Genes and Cerebellar Neurogenesis in the Ventricular Zone and Upper Rhombic Lip. In: Manto, M., Schmahmann, J.D., Rossi, F., Gruol, D.L., Koibuchi, N. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1333-8_2

Download citation

Publish with us

Policies and ethics