Skip to main content
SpringerLink
Log in

Roof Plate in Cerebellar Neurogenesis

  • Living reference work entry
  • First Online:
Handbook of the Cerebellum and Cerebellar Disorders

  • 96 Accesses

Abstract

The roof plate is a distinct group of cells located at the dorsal midline of the developing central nervous system that extends along its entire anterior-posterior axis. In the developing hindbrain, most of the roof plate broadens into a simple epithelial layer covering the dorsal opening of the 4th ventricle. As development proceeds, the 4th ventricle roof plate differentiates into the choroid plexus epithelium, which produces cerebrospinal fluid and serves as a blood-cerebrospinal fluid barrier. A growing amount of evidence indicates that both the 4th ventricle roof plate and its later derivative the hindbrain choroid plexus produce various secreted molecules that regulate development of the adjacent cerebellum. Bone morphogenetic proteins secreted from the roof plate are crucial to the induction of the cerebellar rhombic lip. Signals from the early roof plate and later secretion of Sonic hedgehog from the choroid plexus promote proliferation of progenitors in the cerebellar ventricular zone. This chapter discusses studies that established the roles of the 4th ventricle roof plate and the hindbrain choroid plexus in cerebellar neurogenesis and the molecular mechanisms of their action.

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

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  • Anthony TE, Klein C, Fishell G et al (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41:881–890

    Article  CAS  PubMed  Google Scholar 

  • Awatramani R, Soriano P, Rodriguez C et al (2003) Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet 35:70–75

    Article  CAS  PubMed  Google Scholar 

  • Briscoe J, Small S (2015) Morphogen rules: design principles of gradient-mediated embryo patterning. Development 142:3996–4009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broom ER, Gilthorpe JD, Butts T et al (2012) The roof plate boundary is a bi-directional organizer of dorsal neural tube and choroid plexus development. Development 139:4261–4270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campo-Paysaa F, Clarke JD, Wingate RJ (2019) Generation of the squamous epithelial roof of the 4th ventricle. elife 8:e38485

    Article  PubMed  PubMed Central  Google Scholar 

  • Caronia G, Wilcoxon J, Feldman P et al (2010) Bone morphogenetic protein signaling in the developing telencephalon controls formation of the hippocampal dentate gyrus and modifies fear-related behavior. J Neurosci 30:6291–6301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerrato V, Parmigiani E, Figueres-Oñate M et al (2018) Multiple origins and modularity in the spatiotemporal emergence of cerebellar astrocyte heterogeneity. PLoS Biol 16:e2005513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng X, Hsu CM, Currle DS et al (2006) Central roles of the roof plate in telencephalic development and holoprosencephaly. J Neurosci 26:7640–7649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng FY, Huang X, Sarangi A et al (2012) Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for hedgehog-driven medulloblastoma formation. PLoS One 7:e35541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chenn A, Walsh CA (2002) Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297:365–369

    Article  CAS  PubMed  Google Scholar 

  • Chesnutt C, Burrus LW, Brown AM et al (2004) Coordinate regulation of neural tube patterning and proliferation by TGFbeta and WNT activity. Dev Biol 274:334–347

    Article  CAS  PubMed  Google Scholar 

  • Chizhikov VV, Millen KJ (2005) Roof plate-dependent patterning of the vertebrate dorsal central nervous system. Dev Biol 277:287–295

    Article  CAS  PubMed  Google Scholar 

  • Chizhikov VV, Millen KJ (2020) Neurogenesis in the cerebellum. In: Rakic P, Rubenstein J (eds) Comprehensive developmental neuroscience. Amsterdam, Netherlands. Elsevier (in press)

    Chapter  Google Scholar 

  • Chizhikov VV, Lindgren AG, Currle DS et al (2006) The roof plate regulates cerebellar cell-type specification and proliferation. Development 133:2793–2804

    Article  CAS  PubMed  Google Scholar 

  • Chizhikov VV, Lindgren AG, Mishima Y et al (2010) Lmx1a regulates fates and location of cells originating from the cerebellar rhombic lip and telencephalic cortical hem. Proc Natl Acad Sci U S A 107:10725–10730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chizhikov VV, Iskusnykh IY, Steshina EY et al (2019) Early dorsomedial tissue interactions regulate gyrification of distal neocortex. Nature Commun 10:5192

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Englund C, Kowalczyk T, Daza RA et al (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  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandes M, Antoine M, Hebert JM (2014) SMAD4 is essential for generating subtypes of neurons during cerebellar development. Dev Biol 365:82–90

    Article  CAS  Google Scholar 

  • Fink AJ, Englund C, Daza RA et al (2006) Development of the deep cerebellar nuclei: transcription factors and cell migration from the rhombic lip. J Neurosci 26:3066–3076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleming JT, He W, Hao C et al (2013) The Purkinje neuron acts as a central regulator of spatially and functionally distinct cerebellar precursors. Dev Cell 27:278–292

    Article  CAS  PubMed  Google Scholar 

  • Goetz SC, Anderson KV (2010) The primary cilium: a signaling centre during vertebrate development. Nat Rev Genet 11:331–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hebert JM, Fishell G (2008) The genetics of early telencephalon patterning: some assembly required. Nat Rev Neurosci 9:678–685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoshino M, Nakamura S, Mori K et al (2005) Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47:201–213

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Ketova T, Fleming JT et al (2009) Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus. Development 136:2535–2543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang X, Liu J, Ketova T et al (2010) Transventricular delivery of sonic hedgehog is essential to cerebellar ventricular zone development. Proc Natl Acad Sci U S A 107:8422–8427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huangfu D, Liu A, Rakeman AS et al (2003) Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426:83–87

    Article  CAS  PubMed  Google Scholar 

  • Hunter NL, Dymecki SM (2007) Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus. Development 134:3449–3460

    Article  CAS  PubMed  Google Scholar 

  • Ille F, Atanasoski S, Falk S et al (2007) Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord. Dev Biol 304:394–408

    Article  CAS  PubMed  Google Scholar 

  • Johansson PA, Irmler M, Acampora D, Beckers J, Simeone A, Götz M (2013) The transcription factor Otx2 regulates choroid plexus development and function. Development 140:1055–1066

    Article  CAS  PubMed  Google Scholar 

  • Kaiser K, Gyllborg D, Procházka J et al (2019) WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis. Nat Commun 10:1498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kiecker C, Lumsden A (2005) Compartments and their boundaries in vertebrate brain development. Nat Rev Neurosci 6:553–564

    Article  CAS  PubMed  Google Scholar 

  • Koshida R, Oishi H, Hamada M et al (2017) MafB is required for development of the hindbrain choroid plexus. Biochem Biophys Res Commun 483:288–293

    Article  CAS  PubMed  Google Scholar 

  • Krizhanovsky V, Ben-Arie N (2006) A novel role for the choroid plexus in BMP-mediated inhibition of differentiation of cerebellar neural progenitors. Mech Dev 123:67–75

    Article  CAS  PubMed  Google Scholar 

  • Landsberg RL, Awatramani RB, Hunter NL et al (2005) Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6. Neuron 48:933–947

    Article  CAS  PubMed  Google Scholar 

  • Lee KJ, Jessell TM (1999) The specification of dorsal cell fates in the vertebrate central nervous system. Annu Rev Neurosci 22:261–294

    Article  CAS  PubMed  Google Scholar 

  • Lehtinen MK, Bjornsson CS, Dymecki SM et al (2013) The choroid plexus and cerebrospinal fluid: emerging roles in development, disease, and therapy. J Neurosci 33:17553–17559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leto K, Arancillo M, Becker EB et al (2016) Consensus paper: cerebellar development. Cerebellum 15:789–828

    Article  PubMed  Google Scholar 

  • Lun MP, Monuki ES, Lehtinen MK (2015a) Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Rev Neurosci 16:445–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lun MP, Johnson MB, Broadbelt KG et al (2015b) Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production. J Neurosci 35:4903–4916

    Article  CAS  PubMed  PubMed Central  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  CAS  PubMed  Google Scholar 

  • Machold RP, Kittell DJ, Fishell GJ (2007) Antagonism between notch and bone morphogenetic protein receptor signaling regulates neurogenesis in the cerebellar rhombic lip. Neural Dev 2:5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Megason SG, McMahon AP (2002) A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129:2087–2098

    CAS  PubMed  Google Scholar 

  • Millen KJ, Steshina EY, Iskusnykh IY et al (2014) Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function. Proc Natl Acad Sci U S A 111:E1777–E1786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mishima Y, Lindgren AG, Chizhikov VV et al (2009) Overlapping function of Lmx1a and Lmx1b in anterior hindbrain roof plate formation and cerebellar growth. J Neurosci 29:11377–11384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panchision DM, Pickel JM, Studer L et al (2001) Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev 15:2094–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park SM, Jang HJ, Lee JH (2019) Roles of primary cilia in the developing brain. Front Cell Neurosci 13:218

    Article  PubMed  PubMed Central  Google Scholar 

  • Parmigiani E, Leto K, Rolando C et al (2015) Heterogeneity and bipotency of astroglial-like cerebellar progenitors along the interneuron and glial lineages. J Neurosci 35:7388–7402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pascual M, Abasolo I, Mingorance-Le Meur A et al (2007) Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Proc Natl Acad Sci U S A 104:5193–5198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin L, Wine-Lee L, Ahn KJ et al (2006) Genetic analyses demonstrate that bone morphogenetic protein signaling is required for embryonic cerebellar development. J Neurosci 15:1896–1905

    Article  CAS  Google Scholar 

  • Schilling K, Oberdick J, Rossi F et al (2008) Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex. Histochem Cell Biol 130:601–615

    Article  CAS  PubMed  Google Scholar 

  • Schüller U, Heine VM, Mao J 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  PubMed Central  CAS  Google Scholar 

  • Seto Y, Nakatani T, Masuyama N et al (2014) Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum. Nat Commun 5:3337

    Article  PubMed  CAS  Google Scholar 

  • Sillitoe RV, Joyner AL (2007) Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu Rev Cell Dev Biol 23:549–577

    Article  CAS  PubMed  Google Scholar 

  • Spassky N, Han YG, Aguilar A et al (2008) Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol 317:246–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sudarov A, Turnbull RK, Kim EJ, Lebel-Potter M, Guillemot F, Joyner AL (2011) Ascl1 genetics reveals insights into cerebellum local circuit assembly. J Neurosci 31:11055–11069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timmer JR, Wang C, Niswander L (2002) BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors. Development 129:2459–2472

    CAS  PubMed  Google Scholar 

  • Tong KK, Kwan KM (2013) Common partner Smad-independent canonical bone morphogenetic protein signaling in the specification process of the anterior rhombic lip during cerebellum development. Mol Cell Biol 33:1925–1937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tong KK, Ma TC, Kwan KM (2015) BMP/Smad signaling and embryonic cerebellum development: stem cell specification and heterogeneity of anterior rhombic lip. Dev Growth Differ 57:121–134

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wizeman JW, Guo Q, Wilion EM et al (2019) Specification of diverse cell types during early neurogenesis of the mouse cerebellum. elife 8:e42388

    Article  PubMed  PubMed Central  Google Scholar 

  • Yamada M, Seto Y, Taya S et al (2014) Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons. J Neurosci 34:4786–4800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamamoto M, McCaffery P, Dräger UC (1996) Influence of the choroid plexus on cerebellar development: analysis of retinoic acid synthesis. Brain Res Dev Brain Res 93:182–190

    Article  CAS  PubMed  Google Scholar 

  • Yang ZJ, Ellis T, Markant SL et al (2008) Medulloblastoma can be initiated by deletion of patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeung J, Goldowitz D (2017) Wls expression in the rhombic lip orchestrates the embryonic development of the mouse cerebellum. Neuroscience 354:30–42

    Article  CAS  PubMed  Google Scholar 

  • Yeung J, Ha TJ, Swanson DJ et al (2014) Wls provides a new compartmental view of the rhombic lip in mouse cerebellar development. J Neurosci 34:12527–12537

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zechner D, Müller T, Wende H et al (2007) Bmp and Wnt/beta-catenin signals control expression of the transcription factor Olig3 and the specification of spinal cord neurons. Dev Biol 303:181–190

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Kwan KM, Mailloux CM et al (2007) LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum. Proc Natl Acad Sci U S A 104:13182–13186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou YX, Zhao M, Li D et al (2003) Cerebellar deficits and hyperactivity in mice lacking Smad4. J Biol Chem 278:42313–42320

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA

    Victor V. Chizhikov

Authors
  1. Victor V. Chizhikov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victor V. Chizhikov .

Editor information

Editors and Affiliations

  1. Bruxelles, Belgium

    Mario Manto

  2. Scripps Research Institute Dept. Neuropharmacology, La Jolla, CA, USA

    Donna Gruol

  3. Dept. Neurology, Harvard Medical School Massachusetts General Hospital, Boston, MA, USA

    Jeremy Schmahmann

  4. Gunma University Dept. Integrative Physiology, Maebashi, Gunma, Japan

    Noriyuki Koibuchi

  5. Dept Pathology & Immunology & Neuro, Baylor College of Medicine Dept Pathology & Immunology & Neuro, Houston, TX, USA

    Roy Sillitoe

Section Editor information

  1. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    Roy V. Sillitoe

  2. Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA

    Roy V. Sillitoe

  3. Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA

    Roy V. Sillitoe

  4. Jan and Dan Duncan Neurological Research Institute of Texas Children’s Hospital, Houston, TX, USA

    Roy V. Sillitoe

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Chizhikov, V.V. (2020). Roof Plate in Cerebellar Neurogenesis. In: Manto, M., Gruol, D., Schmahmann, J., Koibuchi, N., Sillitoe, R. (eds) Handbook of the Cerebellum and Cerebellar Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-97911-3_4-2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-97911-3_4-2

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-97911-3

  • Online ISBN: 978-3-319-97911-3

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation