Skip to main content

Specification of Granule Cells and Purkinje Cells

  • Reference work entry
Handbook of the Cerebellum and Cerebellar Disorders

Abstract

Granule cells and Purkinje cells are the major populations of neurons in the cerebellum. Their specification depends on a combination of regional identity and spatiotemporal cues. These are conferred by patterning systems in the early embryo that determine anteroposterior and dorsoventral positional coordinates and an age-dependent signal (or signals) whose nature is obscure. While a number of important questions remain about the nature of cerebellar progenitor pools and their precise boundaries, a variety of fate-mapping and genetic approaches have indicated that both granule cells and Purkinje cells arise from different dorsoventral domains within hindbrain rhombomere 1. Unusually, granule cell precursors undergo a subsequent transit amplification stage regulated by Purkinje cell signals, within a transient superficial germinal layer. Recent evolutionary insights suggest that this phase of Sonic hedgehog-dependent transit amplification is only found in amniotes. Evolutionarily, since secondary proliferation arose independently of granule cell specification, it is likely to be an adaptation purely for postspecification regulation of granule cell numbers.

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

Access this chapter

Institutional subscriptions

References

  • Acampora D, Mazan S, Lallemand Y, Avantaggiato V, Maury M, Simeone A, Brulet P (1995) Forebrain and midbrain regions are deleted in Otx2−/− mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121:3279–3290

    PubMed  CAS  Google Scholar 

  • Alder J, Cho NK, Hatten ME (1996) Embryonic precursor cells from the rhombic lip are specified to a cerebellar granule neuron identity. Neuron 17:389–399

    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 

  • Alexandre P, Wassef M (2003) The isthmic organizer links anteroposterior and dorsoventral patterning in the mid/hindbrain by generating roof plate structures. Development 130:5331–5338

    Article  PubMed  CAS  Google Scholar 

  • Altman J, Bayer SA (1985) Embryonic development of the rat cerebellum. III. Regional differences in the time of origin, migration, and settling of Purkinje cells. J Comp Neurol 231:42–65

    Article  PubMed  CAS  Google Scholar 

  • Apps R, Garwicz M (2005) Anatomical and physiological foundations of cerebellar information processing. Nat Rev Neurosci 6:297–311

    Article  PubMed  CAS  Google Scholar 

  • Baader SL, Schilling ML, Rosengarten B, Pretsch W, Teutsch HF, Oberdick J, Schilling K (1996) Purkinje cell lineage and the topographic organization of the cerebellar cortex: a view from X inactivation mosaics. Dev Biol 174:393–406

    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 

  • 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 

  • Braitenberg V (1961) Functional interpretation of cerebellar histology. Nature 190:539–540

    Article  Google Scholar 

  • Brand M, Heisenberg CP, Jiang YJ, Beuchle D, Lun K, Furutani-Seiki M, Granato M, Haffter P, Hammerschmidt M, Kane DA et al (1996) Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain. Development 123:179–190

    PubMed  CAS  Google Scholar 

  • Butler A, Hodos W (1996) Comparative vertebrate neuroanatomy: evolution and adaptation. Wiley, New York

    Google Scholar 

  • Butts T, Chaplin N, Wingate RJ (2011) Can clues from evolution unlock the molecular development of the cerebellum? Mol Neurobiol 43:67–76

    Article  PubMed  CAS  Google Scholar 

  • Cajal PRy (1891) El encéfalo de los reptiles: Trabajo del Laboratorio. Laboratorio de Histología, Zaragoza

    Google Scholar 

  • Cajal SRy (1894) Les nouvelles idées sur la structure du système nerveux chez l’homme et chez les vertébrés. C. Reinwald & Cie, Paris

    Book  Google Scholar 

  • Cajal SRy (1911) Histologie du système nerveux de l’hommme et des vertébrés. A. Maloine, Paris

    Google Scholar 

  • Chaplin N, Tendeng C, Wingate RJ (2010) Absence of an external germinal layer in zebrafish and shark reveals a distinct, anamniote ground plan of cerebellum development. J Neurosci 30:3048–3057

    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 

  • Chizhikov VV, Lindgren AG, Mishima Y, Roberts RW, Aldinger KA, Miesegaes GR, Currle DS, Monuki ES, Millen KJ (2010) Lmx1a regulates fates and location of cells originating from the cerebellar rhombic lip and telencephalic cortical hem. Proc Natl Acad Sci USA 107:10725–10730

    Article  PubMed  CAS  Google Scholar 

  • Chizhikov VV, Millen KJ (2004) Mechanisms of roof plate formation in the vertebrate CNS. Nat Rev Neurosci 5:808–812

    Article  PubMed  CAS  Google Scholar 

  • Clarke JD, Erskine L, Lumsden A (1998) Differential progenitor dispersal and the spatial origin of early neurons can explain the predominance of single-phenotype clones in the chick hindbrain. Dev Dyn 212:14–26

    Article  PubMed  CAS  Google Scholar 

  • Corrales JD, Blaess S, Mahoney EM, Joyner AL (2006) The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development 133:1811–1821

    Article  PubMed  CAS  Google Scholar 

  • Corrales JD, Rocco GL, Blaess S, Guo Q, Joyner AL (2004) Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development. Development 131:5581–5590

    Article  PubMed  CAS  Google Scholar 

  • Currle DS, Cheng X, Hsu CM, Monuki ES (2005) Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia formation. Development 132:3549–3559

    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 

  • Dean P, Porrill J, Ekerot CF, Jorntell H (2010) The cerebellar microcircuit as an adaptive filter: experimental and computational evidence. Nat Rev Neurosci 11:30–43

    Article  PubMed  CAS  Google Scholar 

  • Eddison M, Toole L, Bell E, Wingate RJ (2004) Segmental identity and cerebellar granule cell induction in rhombomere 1. BMC Biol 2:14

    Article  PubMed  CAS  Google Scholar 

  • Ellison DW, Clifford SC, Gajjar A, Gilbertson RJ (2003) What’s new in neuro-oncology? Recent advances in medulloblastoma. Eur J Paediatr Neurol 7:53–66

    Article  PubMed  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 

  • Espinosa JS, Luo L (2008) Timing neurogenesis and differentiation: insights from quantitative clonal analyses of cerebellar granule cells. J Neurosci 28:2301–2312

    Article  PubMed  CAS  Google Scholar 

  • Fernandez C, Tatard VM, Bertrand N, Dahmane N (2010) Differential modulation of Sonic-hedgehog-induced cerebellar granule cell precursor proliferation by the IGF signaling network. Dev Neurosci 32:59–70

    Article  PubMed  CAS  Google Scholar 

  • Fink AJ, Englund C, Daza RA, Pham D, Lau C, Nivison M, Kowalczyk T, Hevner RF (2006) Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J Neurosci 26:3066–3076

    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 

  • Foucher I, Mione M, Simeone A, Acampora D, Bally-Cuif L, Houart C (2006) Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants. Development 133:1891–1900

    Article  PubMed  CAS  Google Scholar 

  • Gavalas A, Davenne M, Lumsden A, Chambon P, Rijli FM (1997) Role of Hoxa-2 in axon pathfinding and rostral hindbrain patterning. Development 124:3693–3702

    PubMed  CAS  Google Scholar 

  • Gilthorpe JD, Papantoniou EK, Chedotal A, Lumsden A, Wingate RJ (2002) The migration of cerebellar rhombic lip derivatives. Development 129:4719–4728

    PubMed  CAS  Google Scholar 

  • Glasgow SM, Henke RM, Macdonald RJ, Wright CV, Johnson JE (2005) Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development 132:5461–5469

    Article  PubMed  CAS  Google Scholar 

  • Gold DA, Baek SH, Schork NJ, Rose DW, Larsen DD, Sachs BD, Rosenfeld MG, Hamilton BA (2003) RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways. Neuron 40:1119–1131

    Article  PubMed  CAS  Google Scholar 

  • Goldowitz D, Hamre KM, Przyborski SA, Ackerman SL (2000) Granule cells and cerebellar boundaries: analysis of Unc5h3 mutant chimeras. J Neurosci 20:4129–4137

    PubMed  CAS  Google Scholar 

  • Gona AG (1972) Morphogenesis of the cerebellum of the frog tadpole during spontaneous metamorphosis. J Comp Neurol 146:133–142

    Article  PubMed  CAS  Google Scholar 

  • Goodrich LV, Milenkovic L, Higgins KM, Scott MP (1997) Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277:1109–1113

    Article  PubMed  CAS  Google Scholar 

  • Hallonet ME, Le Douarin NM (1993) Tracing neuroepithelial cells of the mesencephalic and metencephalic alar plates during cerebellar ontogeny in quail-chick chimaeras. Eur J Neurosci 5:1145–1155

    Article  PubMed  CAS  Google Scholar 

  • Hallonet ME, Teillet MA, Le Douarin NM (1990) A new approach to the development of the cerebellum provided by the quail-chick marker system. Development 108:19–31

    PubMed  CAS  Google Scholar 

  • Hawkes R, Beierbach E, Tan SS (1999) Granule cell dispersion is restricted across transverse boundaries in mouse chimeras. Eur J Neurosci 11:3800–3808

    Article  PubMed  CAS  Google Scholar 

  • Hawkes R, Herrup K (1995) Aldolase C/zebrin II and the regionalization of the cerebellum. J Mol Neurosci 6:147–158

    Article  PubMed  CAS  Google Scholar 

  • Helms AW, Johnson JE (1998) Progenitors of dorsal commissural interneurons are defined by MATH1 expression. Development 125:919–928

    PubMed  CAS  Google Scholar 

  • Helms AW, Johnson JE (2003) Specification of dorsal spinal cord interneurons. Curr Opin Neurobiol 13:42–49

    Article  PubMed  CAS  Google Scholar 

  • Holland LZ, Holland ND (1999) Chordate origins of the vertebrate central nervous system. Curr Opin Neurobiol 9:596–602

    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 et al (2005) Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47:201–213

    Article  PubMed  CAS  Google Scholar 

  • Irving C, Mason I (2000) Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. Development 127:177–186

    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 (1996) Engrailed, Wnt and Pax genes regulate midbrain–hindbrain development. Trends Genet 12:15–20

    Article  PubMed  CAS  Google Scholar 

  • Kani S, Bae YK, Shimizu T, Tanabe K, Satou C, Parsons MJ, Scott E, Higashijima S, Hibi M (2010) Proneural gene-linked neurogenesis in zebrafish cerebellum. Dev Biol 343:1–17

    Article  PubMed  CAS  Google Scholar 

  • Kenney AM, Cole MD, Rowitch DH (2003) Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130:15–28

    Article  PubMed  CAS  Google Scholar 

  • Kenney AM, Widlund HR, Rowitch DH (2004) Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development 131:217–228

    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 

  • Klein C, Butt SJ, Machold RP, Johnson JE, Fishell G (2005) Cerebellum- and forebrain-derived stem cells possess intrinsic regional character. Development 132:4497–4508

    Article  PubMed  CAS  Google Scholar 

  • Koibuchi N (2008) The role of thyroid hormone on cerebellar development. Cerebellum 7:530–533

    Article  PubMed  CAS  Google Scholar 

  • Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J et al (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS ONE 3:e3088

    Article  PubMed  CAS  Google Scholar 

  • Koster RW, Fraser SE (2006) FGF signaling mediates regeneration of the differentiating cerebellum through repatterning of the anterior hindbrain and reinitiation of neuronal migration. J Neurosci 26:7293–7304

    Article  PubMed  CAS  Google Scholar 

  • Larouche M, Hawkes R (2006) From clusters to stripes: the developmental origins of adult cerebellar compartmentation. Cerebellum 5:77–88

    Article  PubMed  CAS  Google Scholar 

  • Le Douarin NM (1993) Embryonic neural chimaeras in the study of brain development. Trends Neurosci 16:64–72

    Article  PubMed  Google Scholar 

  • Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB, Johnson JE, Wechsler-Reya RJ (2005) Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8:723–729

    Article  PubMed  CAS  Google Scholar 

  • Lee KJ, Dietrich P, Jessell TM (2000) Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403:734–740

    Article  PubMed  CAS  Google Scholar 

  • Lee KJ, Mendelsohn M, Jessell TM (1998) Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev 12:3394–3407

    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 

  • Lin JC, Cai L, Cepko CL (2001) The external granule layer of the developing chick cerebellum generates granule cells and cells of the isthmus and rostral hindbrain. J Neurosci 21:159–168

    PubMed  CAS  Google Scholar 

  • Lin JC, Cepko CL (1999) Biphasic dispersion of clones containing Purkinje cells and glia in the developing chick cerebellum. Dev Biol 211:177–197

    Article  PubMed  CAS  Google Scholar 

  • Lisney TJ, Yopak KE, Montgomery JC, Collin SP (2008) Variation in brain organization and cerebellar foliation in chondrichthyans: batoids. Brain Behav Evol 72:262–282

    Article  PubMed  Google Scholar 

  • Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274:1109–1115

    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 

  • 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 

  • Matsumoto K, Nishihara S, Kamimura M, Shiraishi T, Otoguro T, Uehara M, Maeda Y, Ogura K, Lumsden A, Ogura T (2004) The prepattern transcription factor Irx2, a target of the FGF8/MAP kinase cascade, is involved in cerebellum formation. Nat Neurosci 7:605–612

    Article  PubMed  CAS  Google Scholar 

  • McConnell SK, Kaznowski CE (1991) Cell cycle dependence of laminar determination in developing neocortex. Science 254:282–285

    Article  PubMed  CAS  Google Scholar 

  • Miesegaes GR, Klisch TJ, Thaller C, Ahmad KA, Atkinson RC, Zoghbi HY (2009) Identification and subclassification of new Atoh1 derived cell populations during mouse spinal cord development. Dev Biol 327:339–351

    Article  PubMed  CAS  Google Scholar 

  • Millet S, Bloch-Gallego E, Simeone A, Alvarado-Mallart RM (1996) The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts. Development 122:3785–3797

    PubMed  CAS  Google Scholar 

  • Millonig JH, Millen KJ, Hatten ME (2000) The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Nature 403:764–769

    Article  PubMed  CAS  Google Scholar 

  • Mizuhara E, Minaki Y, Nakatani T, Kumai M, Inoue T, Muguruma K, Sasai Y, Ono Y (2010) Purkinje cells originate from cerebellar ventricular zone progenitors positive for Neph3 and E-cadherin. Dev Biol 338:202–214

    Article  PubMed  CAS  Google Scholar 

  • Morales D, Hatten ME (2006) Molecular markers of neuronal progenitors in the embryonic cerebellar anlage. J Neurosci 26:12226–12236

    Article  PubMed  CAS  Google Scholar 

  • Nielsen CM, Dymecki SM (2010) Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus. Dev Biol 340:430–437

    Article  PubMed  CAS  Google Scholar 

  • Nieuwenhuys R, Nicholson C (1969) A survey of the general morphology, the fiber connections, and the possible functional significance of the gigantocerebellum of mormyrid fishes. In: Llinás R (ed) Neurobiology of cerebellar evolution and development. American Medical Association, Chicago, pp 107–134

    Google Scholar 

  • Nieuwenhuys R, ten Donkelaar HJ, Nicholson C (1998) The central nervous system of vertebrates. Springer, Berlin

    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 

  • Reifers F, Bohli H, Walsh EC, Crossley PH, Stainier DY, Brand M (1998) Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. Development 125:2381–2395

    PubMed  CAS  Google Scholar 

  • Rieger S, Senghaas N, Walch A, Koster RW (2009) Cadherin-2 controls directional chain migration of cerebellar granule neurons. PLoS Biol 7:e1000240

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez CI, Dymecki SM (2000) Origin of the precerebellar system. Neuron 27:475–486

    Article  PubMed  CAS  Google Scholar 

  • Rose MF, Ahmad KA, Thaller C, Zoghbi HY (2009) Excitatory neurons of the proprioceptive, interoceptive, and arousal hindbrain networks share a developmental requirement for Math1. Proc Natl Acad Sci USA 106:22462–22467

    Article  PubMed  CAS  Google Scholar 

  • Ryder EF, Cepko CL (1994) Migration patterns of clonally related granule cells and their progenitors in the developing chick cerebellum. Neuron 12:1011–1028

    Article  PubMed  CAS  Google Scholar 

  • Sato T, Joyner AL (2009) The duration of Fgf8 isthmic organizer expression is key to patterning different tectal-isthmo-cerebellum structures. Development 136:3617–3626

    Article  PubMed  CAS  Google Scholar 

  • Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y et al (2008) Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–134

    Article  PubMed  CAS  Google Scholar 

  • Sgaier SK, Millet S, Villanueva MP, Berenshteyn F, Song C, Joyner AL (2005) Morphogenetic and cellular movements that shape the mouse cerebellum; insights from genetic fate mapping. Neuron 45:27–40

    PubMed  CAS  Google Scholar 

  • Sultan F (2005) Why some bird brains are larger than others. Curr Biol 15:R649–R650

    Article  PubMed  CAS  Google Scholar 

  • Sultan F, Glickstein M (2007) The cerebellum: comparative and animal studies. Cerebellum 6:168–176

    Article  PubMed  Google Scholar 

  • Swanson DJ, Goldowitz D (2011) Experimental Sey mouse chimeras reveal the developmental deficiencies of Pax6-null granule cells in the postnatal cerebellum. Dev Biol 351(1):1–12

    Article  PubMed  CAS  Google Scholar 

  • Wada H, Saiga H, Satoh N, Holland PW (1998) Tripartite organization of the ancestral chordate brain and the antiquity of placodes: insights from ascidian Pax-2/5/8, Hox and Otx genes. Development 125:1113–1122

    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 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 

  • Watt AJ, Cuntz H, Mori M, Nusser Z, Sjostrom PJ, Hausser M (2009) Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity. Nat Neurosci 12:463–473

    Article  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 

  • Wilson LJ, Myat A, Sharma A, Maden M, Wingate RJ (2007) Retinoic acid is a potential dorsalising signal in the late embryonic chick hindbrain. BMC Dev Biol 7:138

    Article  PubMed  CAS  Google Scholar 

  • Wilson LJ, Wingate RJ (2006) Temporal identity transition in the avian cerebellar rhombic lip. Dev Biol 297:508–521

    Article  PubMed  CAS  Google Scholar 

  • Wingate R (2005) Math-Map(ic)s. Neuron 48:1–4

    Article  PubMed  CAS  Google Scholar 

  • Wingate RJ, Lumsden A (1996) Persistence of rhombomeric organisation in the postsegmental hindbrain. Development 122:2143–2152

    PubMed  CAS  Google Scholar 

  • Wingate RJT (2001) The rhombic lip and early cerebellar development. Curr Opin Neurobiol 11:82–88

    Article  PubMed  CAS  Google Scholar 

  • Wingate RJT, Hatten ME (1999) The role of the rhombic lip in avian cerebellum development. Development 126:4395–4404

    PubMed  CAS  Google Scholar 

  • Wurst W, Auerbach AB, Joyner AL (1994) Multiple developmental defects in Engrailed-1 mutant mice: an early mid- hindbrain deletion and patterning defects in forelimbs and sternum. Development 120:2065–2075

    PubMed  CAS  Google Scholar 

  • Xu J, Liu Z, Ornitz DM (2000) Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures. Development 127:1833–1843

    PubMed  CAS  Google Scholar 

  • Yamamoto M, Zhang J, Smith D, Hayakawa Y, McCaffery P (2003) A critical period for retinoic acid teratogenesis and loss of neurophilic migration of pontine nuclei neurons. Mech Dev 120:701–709

    Article  PubMed  CAS  Google Scholar 

  • Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M, Schuller U, Machold R, Fishell G, Rowitch DH et al (2008) Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–145

    Article  PubMed  CAS  Google Scholar 

  • Yopak KE, Lisney TJ, Collin SP, Montgomery JC (2007) Variation in brain organization and cerebellar foliation in chondrichthyans: sharks and holocephalans. Brain Behav Evol 69:280–300

    Article  PubMed  Google Scholar 

  • Yopak KE, Montgomery JC (2008) Brain organization and specialization in deep-sea chondrichthyans. Brain Behav Evol 71:287–304

    Article  PubMed  Google Scholar 

  • Zhang L, Goldman JE (1996) Generation of cerebellar interneurons from dividing progenitors in white matter. Neuron 16:47–54

    Article  PubMed  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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard J. T. Wingate .

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

Butts, T., Wilson, L., Wingate, R.J.T. (2013). Specification of Granule Cells and Purkinje Cells. 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_6

Download citation

Publish with us

Policies and ethics