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The guanine nucleotide exchange factor Vav3 regulates differentiation of progenitor cells in the developing mouse retina

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An Erratum to this article was published on 12 March 2015

Abstract

The seven main cell types in the mammalian retina arise from multipotent retinal progenitor cells, a process that is tightly regulated by intrinsic and extrinsic signals. However, the molecular mechanisms that control proliferation, differentiation and cell-fate decisions of retinal progenitor cells are not fully understood yet. Here, we report that the guanine nucleotide exchange factor Vav3, a regulator of Rho-GTPases, is involved in retinal development. We demonstrate that Vav3 is expressed in the mouse retina during the embryonic period. In order to study the role of Vav3 in the developing retina, we generate Vav3-deficient mice. The loss of Vav3 results in an accelerated differentiation of retinal ganglion cells and cone photoreceptors during early and late embryonic development. We provide evidence that more retinal progenitor cells express the late progenitor marker Sox9 in Vav3-deficient mice than in wild-types. This premature differentiation is compensated during the postnatal period and late-born cell types such as bipolar cells and Müller glia display normal numbers. Taken together, our data imply that Vav3 is a regulator of retinal progenitor cell differentiation, thus highlighting a novel role for guanine nucleotide exchange factors in retinogenesis.

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References

  • Agathocleous M, Harris WA (2009) From progenitors to differentiated cells in the vertebrate retina. Annu Rev Cell Dev Biol 25:45–69

    Article  CAS  PubMed  Google Scholar 

  • Agathocleous M, Locker M, Harris WA, Perron M (2007) A general role of hedgehog in the regulation of proliferation. Cell Cycle 6:156–159

    Article  CAS  PubMed  Google Scholar 

  • Aoki K, Nakamura T, Fujikawa K, Matsuda M (2005) Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells. Mol Biol Cell 16:2207–2217

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baas D, Bumsted KM, Martinez JA, Vaccarino FM, Wikler KC, Barnstable CJ (2000) The subcellular localization of Otx2 is cell-type specific and developmentally regulated in the mouse retina. Brain Res Mol Brain Res 78:26–37

    Article  CAS  PubMed  Google Scholar 

  • Bai N, Hayashi H, Aida T, Namekata K, Harada T, Mishina M, Tanaka K (2013) Dock3 interaction with a glutamate-receptor NR2D subunit protects neurons from excitotoxicity. Mol Brain 6:22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bard JL, Kaufman MH, Dubreuil C, Brune RM, Burger A, Baldock RA, Davidson DR (1998)An internet-accessible database of mouse developmental anatomy based on a systematic nomenclature. Mech Dev 74:111–120

    Article  CAS  PubMed  Google Scholar 

  • Besser M, Jagatheaswaran M, Reinhard J, Schaffelke P, Faissner A (2012) Tenascin C regulates proliferation and differentiation processes during embryonic retinogenesis and modulates the de-differentiation capacity of Muller glia by influencing growth factor responsiveness and the extracellular matrix compartment. Dev Biol 369:163–176

    Article  CAS  PubMed  Google Scholar 

  • Brown NL, Patel S, Brzezinski J, Glaser T (2001) Math5 is required for retinal ganglion cell and optic nerve formation. Development 128:2497–2508

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brzezinski JAT, Lamba DA, Reh TA (2010) Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development. Development 137:619–629

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burmeister M, Novak J, Liang MY, Basu S, Ploder L, Hawes NL, Vidgen D, Hoover F, Goldman D, Kalnins VI, Roderick TH, Taylor BA, Hankin MH, McInnes RR (1996) Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat Genet 12:376–384

    Article  CAS  PubMed  Google Scholar 

  • Bustelo XR (2001) Vav proteins, adaptors and cell signaling. Oncogene 20:6372–6381

    Article  CAS  PubMed  Google Scholar 

  • Cann GM, Bradshaw AD, Gervin DB, Hunter AW, Clegg DO (1996) Widespread expression of beta1 integrins in the developing chick retina: evidence for a role in migration of retinal ganglion cells. Dev Biol 180:82–96

    Article  CAS  PubMed  Google Scholar 

  • Carter-Dawson LD, LaVail MM (1979) Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine. J Comp Neurol 188:263–272

    Article  CAS  PubMed  Google Scholar 

  • Cepko CL, Austin CP, Yang X, Alexiades M, Ezzeddine D (1996) Cell fate determination in the vertebrate retina. Proc Natl Acad Sci U S A 93:589–595

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cherfils J, Chardin P (1999)GEFs: structural basis for their activation of small GTP-binding proteins.Trends Biochem Sci 24:306–311

    Article  CAS  PubMed  Google Scholar 

  • Cowan CW, Shao YR, Sahin M, Shamah SM, Lin MZ, Greer PL, Gao S, Griffith EC, Brugge JS, Greenberg ME (2005) Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 46:205–217

    Article  CAS  PubMed  Google Scholar 

  • Dyer MA, Cepko CL (2001) Regulating proliferation during retinal development. Nat Rev Neurosci 2:333–342

    Article  CAS  PubMed  Google Scholar 

  • Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003) Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat Genet 34:53–58

    Article  CAS  PubMed  Google Scholar 

  • Eguchi K, Yoshioka Y, Yoshida H, Morishita K, Miyata S, Hiai H, Yamaguchi M (2013) The Drosophila DOCK family protein sponge is involved in differentiation of R7 photoreceptor cells. Exp Cell Res 319:2179–2195

    Article  CAS  PubMed  Google Scholar 

  • Faccio R, Teitelbaum SL, Fujikawa K, Chappel J, Zallone A, Tybulewicz VL, Ross FP, Swat W (2005) Vav3 regulates osteoclast function and bone mass. Nat Med 11:284–290

    Article  CAS  PubMed  Google Scholar 

  • Faissner A, Clement A, Lochter A, Streit A, Mandl C, Schachner M (1994) Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties. J Cell Biol 126:783–799

    Article  CAS  PubMed  Google Scholar 

  • Friedlander DR, Milev P, Karthikeyan L, Margolis RK, Margolis RU, Grumet M (1994) The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and neurite outgrowth. J Cell Biol 125:669–680

    Article  CAS  PubMed  Google Scholar 

  • Fujikawa K, Inoue Y, Sakai M, Koyama Y, Nishi S, Funada R, Alt FW, Swat W (2002) Vav3 is regulated during the cell cycle and effects cell division. Proc Natl Acad Sci U S A 99:4313–4318

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fujikawa K, Miletic AV, Alt FW, Faccio R, Brown T, Hoog J, Fredericks J, Nishi S, Mildiner S, Moores SL, Brugge J, Rosen FS, Swat W (2003) Vav1/2/3-null mice define an essential role for Vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells. J Exp Med 198:1595–1608

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fujikawa K, Iwata T, Inoue K, Akahori M, Kadotani H, Fukaya M, Watanabe M, Chang Q, Barnett EM, Swat W (2010) VAV2 and VAV3 as candidate disease genes for spontaneous glaucoma in mice and humans. PLoS One 5:e9050

    Article  PubMed Central  PubMed  Google Scholar 

  • Gakidis MA, Cullere X, Olson T, Wilsbacher JL, Zhang B, Moores SL, Ley K, Swat W, Mayadas T, Brugge JS (2004) Vav GEFs are required for beta2 integrin-dependent functions of neutrophils. J Cell Biol 166:273–282

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gan L, Xiang M, Zhou L, Wagner DS, Klein WH, Nathans J (1996) POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells. Proc Natl Acad Sci U S A 93:3920–3925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Garcion E, Halilagic A, Faissner A, ffrench-Constant C (2004) Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development 131:3423–3432

    Article  CAS  PubMed  Google Scholar 

  • Hatakeyama J, Kageyama R (2004) Retinal cell fate determination and bHLH factors. Semin Cell Dev Biol 15:83–89

    Article  CAS  PubMed  Google Scholar 

  • Hatakeyama J, Tomita K, Inoue T, Kageyama R (2001) Roles of homeobox and bHLH genes in specification of a retinal cell type. Development 128:1313–1322

    CAS  PubMed  Google Scholar 

  • Henning S, Cleverley S (1999) Small GTPases in lymphocyte biology: Rho proteins take center stage. Immunol Res 20:29–42

    Article  CAS  PubMed  Google Scholar 

  • Herder C, Swiercz JM, Muller C, Peravali R, Quiring R, Offermanns S, Wittbrodt J, Loosli F (2013) ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation. Development 140:2787–2797

    Article  CAS  PubMed  Google Scholar 

  • Horvat-Brocker A, Reinhard J, Illes S, Paech T, Zoidl G, Harroch S, Distler C, Knyazev P, Ullrich A, Faissner A (2008) Receptor protein tyrosine phosphatases are expressed by cycling retinal progenitor cells and involved in neuronal development of mouse retina. Neuroscience 152:618–645

    Article  CAS  PubMed  Google Scholar 

  • Hunter SG, Zhuang G, Brantley-Sieders D, Swat W, Cowan CW, Chen J (2006) Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis. Mol Cell Biol 26:4830–4842

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Inatani M, Tanihara H (2002) Proteoglycans in retina. Prog Retin Eye Res 21:429–447

    Article  CAS  PubMed  Google Scholar 

  • Inatani M, Honjo M, Otori Y, Oohira A, Kido N, Tano Y, Honda Y, Tanihara H (2001) Inhibitory effects of neurocan and phosphacan on neurite outgrowth from retinal ganglion cells in culture. Invest Ophthalmol Vis Sci 42:1930–1938

    CAS  PubMed  Google Scholar 

  • Karus M, Denecke B, ffrench-Constant C, Wiese S, Faissner A (2011) The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification. Development 138:5321–5331

    Article  CAS  PubMed  Google Scholar 

  • Katzav S (2009) Vav1: a hematopoietic signal transduction molecule involved in human malignancies. Int J Biochem Cell Biol 41:1245–1248

    Article  CAS  PubMed  Google Scholar 

  • Kazanis I, Belhadi A, Faissner A, ffrench-Constant C (2007) The adult mouse subependymal zone regenerates efficiently in the absence of tenascin-C. J Neurosci 27:13991–13996

  • Klausmeyer A, Garwood J, Faissner A (2007) Differential expression of phosphacan/RPTPbeta isoforms in the developing mouse visual system. J Comp Neurol 504:659–679

    Article  CAS  PubMed  Google Scholar 

  • Kusuhara S, Fukushima Y, Fukuhara S, Jakt LM, Okada M, Shimizu Y, Hata M, Nishida K, Negi A, Hirashima M, Mochizuki N, Nishikawa S, Uemura A (2012) Arhgef15 promotes retinal angiogenesis by mediating VEGF-induced Cdc42 activation and potentiating RhoJ inactivation in endothelial cells. PLoS One 7:e45858

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leu ST, Jacques SA, Wingerd KL, Hikita ST, Tolhurst EC, Pring JL, Wiswell D, Kinney L, Goodman NL, Jackson DY, Clegg DO (2004) Integrin alpha4beta1 function is required for cell survival in developing retina. Dev Biol 276:416–430

    Article  CAS  PubMed  Google Scholar 

  • Lilienbaum A, Reszka AA, Horwitz AF, Holt CE (1995) Chimeric integrins expressed in retinal ganglion cells impair process outgrowth in vivo. Mol Cell Neurosci 6:139–152

    Article  CAS  PubMed  Google Scholar 

  • Lillien L, Cepko C (1992) Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF alpha. Development 115:253–266

    CAS  PubMed  Google Scholar 

  • Lillien L, Wancio D (1998) Changes in epidermal growth factor receptor expression and competence to generate glia regulate timing and choice of differentiation in the retina. Mol Cellular Neurosci 10:296–308

    Article  CAS  Google Scholar 

  • Liu IS, Chen JD, Ploder L, Vidgen D, van der Kooy D, Kalnins VI, McInnes RR (1994) Developmental expression of a novel murine homeobox gene (Chx10): evidence for roles in determination of the neuroretina and inner nuclear layer. Neuron 13:377–393

    Article  CAS  PubMed  Google Scholar 

  • Locker M, Agathocleous M, Amato MA, Parain K, Harris WA, Perron M (2006) Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors. Genes Dev 20:3036–3048

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mao CA, Kiyama T, Pan P, Furuta Y, Hadjantonakis AK, Klein WH (2008) Eomesodermin, a target gene of Pou4f2, is required for retinal ganglion cell and optic nerve development in the mouse. Development 135:271–280

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marquardt T, Gruss P (2002) Generating neuronal diversity in the retina: one for nearly all. Trends Neurosci 25:32–38

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Morales JR, Del Bene F, Nica G, Hammerschmidt M, Bovolenta P, Wittbrodt J (2005) Differentiation of the vertebrate retina is coordinated by an FGF signaling center. Dev Cell 8:565–574

    Article  CAS  PubMed  Google Scholar 

  • Miletic AV, Graham DB, Montgrain V, Fujikawa K, Kloeppel T, Brim K, Weaver B, Schreiber R, Xavier R, Swat W (2007) Vav proteins control MyD88-dependent oxidative burst. Blood 109:3360–3368

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mitchell DC, Bryan BA, Liu JP, Liu WB, Zhang L, Qu J, Zhou X, Liu M, Li DW (2007) Developmental expression of three small GTPases in the mouse eye. Mol Vis 13:1144–1153

    PubMed Central  CAS  PubMed  Google Scholar 

  • Moores SL, Selfors LM, Fredericks J, Breit T, Fujikawa K, Alt FW, Brugge JS, Swat W (2000) Vav family proteins couple to diverse cell surface receptors. Mol Cell Biol 20:6364–6373

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Moritz S, Lehmann S, Faissner A, von Holst A (2008) An induction gene trap screen in neural stem cells reveals an instructive function of the niche and identifies the splicing regulator sam68 as a tenascin-C-regulated target gene. Stem Cells 26:2321–2331

    Article  CAS  PubMed  Google Scholar 

  • Morrow EM, Furukawa T, Lee JE, Cepko CL (1999) NeuroD regulates multiple functions in the developing neural retina in rodent. Development 126:23–36

    CAS  PubMed  Google Scholar 

  • Movilla N, Bustelo XR (1999) Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins. Mol Cell Biol 19:7870–7885

    PubMed Central  CAS  PubMed  Google Scholar 

  • Namekata K, Kimura A, Kawamura K, Guo X, Harada C, Tanaka K, Harada T (2013) Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma. Cell Death Differ 20:1250–1256

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nishida A, Furukawa A, Koike C, Tano Y, Aizawa S, Matsuo I, Furukawa T (2003) Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat Neurosci 6:1255–1263

    Article  CAS  PubMed  Google Scholar 

  • Ohsawa R, Kageyama R (2008) Regulation of retinal cell fate specification by multiple transcription factors. Brain Res 1192:90–98

    Article  CAS  PubMed  Google Scholar 

  • Oohira A, Matsui F, Katoh-Semba R (1991) Inhibitory effects of brain chondroitin sulfate proteoglycans on neurite outgrowth from PC12D cells. J Neurosci 11:822–827

    CAS  PubMed  Google Scholar 

  • Pearce AC, McCarty OJ, Calaminus SD, Vigorito E, Turner M, Watson SP (2007) Vav family proteins are required for optimal regulation of PLCgamma2 by integrin alphaIIbbeta3. Biochem J 401:753–761

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36

    Article  PubMed Central  PubMed  Google Scholar 

  • Poche RA, Furuta Y, Chaboissier MC, Schedl A, Behringer RR (2008) Sox9 is expressed in mouse multipotent retinal progenitor cells and functions in Muller glial cell development. J Comp Neurol 510:237–250

    Article  PubMed  Google Scholar 

  • Pollard SM, Wallbank R, Tomlinson S, Grotewold L, Smith A (2008) Fibroblast growth factor induces a neural stem cell phenotype in foetal forebrain progenitors and during embryonic stem cell differentiation. Mol Cell Neurosci 38:393–403

    Article  CAS  PubMed  Google Scholar 

  • Quevedo C, Sauzeau V, Menacho-Marquez M, Castro-Castro A, Bustelo XR (2010) Vav3-deficient mice exhibit a transient delay in cerebellar development. Mol Biol Cell 21:1125–1139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Quina LA, Pak W, Lanier J, Banwait P, Gratwick K, Liu Y, Velasquez T, O'Leary DD, Goulding M, Turner EE (2005) Brn3a-expressing retinal ganglion cells project specifically to thalamocortical and collicular visual pathways. J Neurosci 25:11595–11604

    Article  CAS  PubMed  Google Scholar 

  • Ray A, Zoidl G, Weickert S, Wahle P, Dermietzel R (2005) Site-specific and developmental expression of pannexin1 in the mouse nervous system. Eur J Neurosci 21:3277–3290

    Article  PubMed  Google Scholar 

  • Ridley AJ, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399

    Article  CAS  PubMed  Google Scholar 

  • Rowan S, Cepko CL (2004) Genetic analysis of the homeodomain transcription factor Chx10 in the retina using a novel multifunctional BAC transgenic mouse reporter. Dev Biol 271:388–402

    Article  CAS  PubMed  Google Scholar 

  • Sakagami H, Katsumata O, Hara Y, Tamaki H, Watanabe M, Harvey RJ, Fukaya M (2013) Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina. J Comp Neurol 521:860–876

    Article  CAS  PubMed  Google Scholar 

  • Sauzeau V, Sevilla MA, Rivas-Elena JV, de Alava E, Montero MJ, Lopez-Novoa JM, Bustelo XR (2006) Vav3 proto-oncogene deficiency leads to sympathetic hyperactivity and cardiovascular dysfunction. Nat Med 12:841–845

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sharma RK, Netland PA (2007) Early born lineage of retinal neurons express class III beta-tubulin isotype. Brain Res 1176:11–17

    Article  CAS  PubMed  Google Scholar 

  • Sherry DM, Blackburn BA (2013) P-Rex2, a Rac-guanine nucleotide exchange factor, is expressed selectively in ribbon synaptic terminals of the mouse retina. BMC Neurosci 14:70

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Solovei I, Kreysing M, Lanctot C, Kosem S, Peichl L, Cremer T, Guck J, Joffe B (2009) Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137:356–368

    Article  CAS  PubMed  Google Scholar 

  • Taranova OV, Magness ST, Fagan BM, Wu Y, Surzenko N, Hutton SR, Pevny LH (2006) SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev 20:1187–1202

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tham M, Ramasamy S, Gan HT, Ramachandran A, Poonepalli A, Yu YH, Ahmed S (2010) CSPG is a secreted factor that stimulates neural stem cell survival possibly by enhanced EGFR signaling. PLoS One 5:e15341

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Toumaniantz G, Ferland-McCollough D, Cario-Toumaniantz C, Pacaud P, Loirand G (2010) The Rho protein exchange factor Vav3 regulates vascular smooth muscle cell proliferation and migration. Cardiovasc Res 86:131–140

    Article  CAS  PubMed  Google Scholar 

  • Tsapara A, Luthert P, Greenwood J, Hill CS, Matter K, Balda MS (2010) The RhoA activator GEF-H1/Lfc is a transforming growth factor-beta target gene and effector that regulates alpha-smooth muscle actin expression and cell migration. Mol Biol Cell 21:860–870

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • von Holst A, Egbers U, Prochiantz A, Faissner A (2007) Neural stem/progenitor cells express 20 tenascin C isoforms that are differentially regulated by Pax6. J Biol Chem 282:9172–9181

    Article  Google Scholar 

  • Wang J, Deretic D (2014) Molecular complexes that direct rhodopsin transport to primary cilia. Prog Retin Eye Res 38:1–19

    Article  PubMed  Google Scholar 

  • Wang Y, Dakubo GD, Thurig S, Mazerolle CJ, Wallace VA (2005) Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development 132:5103–5113

    Article  CAS  PubMed  Google Scholar 

  • Xiong B, Bayat V, Jaiswal M, Zhang K, Sandoval H, Charng WL, Li T, David G, Duraine L, Lin YQ, Neely GG, Yamamoto S, Bellen HJ (2012) Crag is a GEF for Rab11 required for rhodopsin trafficking and maintenance of adult photoreceptor cells. PLoS Biol 10:e1001438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Young RW (1985a) Cell differentiation in the retina of the mouse. Anat Rec 212:199–205

    Article  CAS  PubMed  Google Scholar 

  • Young RW (1985b) Cell proliferation during postnatal development of the retina in the mouse. Brain Res 353:229–239

    Article  CAS  PubMed  Google Scholar 

  • Zou W, Teitelbaum SL (2010) Integrins, growth factors, and the osteoclast cytoskeleton. Ann N Y Acad Sci 1192:27–31

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Majury Kandasamy and Lars Roll for critical reading of the manuscript and helpful discussions. We gratefully acknowledge the excellent technical assistance of Anke Mommsen and Marion Voelzkow.

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Authors and Affiliations

  1. Department of Cell Morphology & Molecular Neurobiology, Ruhr-University Bochum, NDEF 05/594 Universitaetsstrasse 150, 44780, Bochum, Germany

    Veronika Luft, Jacqueline Reinhard & Andreas Faissner

  2. International Graduate School of Neuroscience (IGSN), FNO 1/116 Universitaetsstrasse 150, 44780, Bochum, Germany

    Veronika Luft

  3. Division of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan

    Masabumi Shibuya

  4. Institute of Biochemistry and Cell Biology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Klaus D. Fischer

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  1. Veronika Luft
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  2. Jacqueline Reinhard
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  3. Masabumi Shibuya
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  4. Klaus D. Fischer
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  5. Andreas Faissner
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Corresponding author

Correspondence to Andreas Faissner.

Additional information

V.L. and J.R. contributed equally to this work.

V.L. was a graduate student of the International Graduate School of Neuroscience (IGSN) of the Ruhr-University Bochum during part of this work. V.L. and J.R. thank the Ruhr-University Research School funded by Germany’s Excellence Initiative for further funding (DFG GSC 98/1) and the German Research Foundation (DFG, SFB 509 and Fa 159/16-1 to A.F.), the Ministry of Innovation, Research and Technology of the Land NRW (Stem Cell Network NRW) and the Ruhr-University (President’s special programme call 2008 to A.F.) for grant support.

The authors declare no competing financial interests.

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Luft, V., Reinhard, J., Shibuya, M. et al. The guanine nucleotide exchange factor Vav3 regulates differentiation of progenitor cells in the developing mouse retina. Cell Tissue Res 359, 423–440 (2015). https://doi.org/10.1007/s00441-014-2050-2

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