Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Mechanisms of roof plate formation in the vertebrate CNS

Nature Reviews Neuroscience volume 5, pages 808–812 (2004)Cite this article

Abstract

The roof plate is an embryonic organizing centre that occupies the dorsal midline of the vertebrate neural tube. During early CNS development, the roof plate produces secreted factors, which control the specification and differentiation of dorsal neuronal cell types. An appreciation of the signalling properties of the roof plate has prompted an enhanced interest in this important organizing centre, and several recent studies have begun to illuminate the molecular mechanisms of roof plate development.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Identification of roof plate cells in the embryonic chick spinal cord by Lmx1a immunofluorescence.
Figure 2: Cell-lineage analysis in the developing dorsal spinal cord.
Figure 3: Generation of roof plate, neural crest and dI1 interneuron progenitors in the early developing spinal cord.

Similar content being viewed by others

References

  1. Lee, K. J. & Jessell, T. M. The specification of dorsal cell fates in the vertebrate central nervous system. Annu. Rev. Neurosci. 22, 261–294 (1999).

    Article  CAS  Google Scholar 

  2. Jessell, T. M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nature Rev. Genet. 1, 20–29 (2000).

    Article  CAS  Google Scholar 

  3. Shirasaki, R. & Pfaff, S. L. Transcriptional codes and the control of neuronal identity. Annu. Rev. Neurosci. 25, 251–281 (2002).

    Article  CAS  Google Scholar 

  4. Marti, E. & Bovolenta, P. Sonic hedgehog in CNS development: one signal, multiple outputs. Trends Neurosci. 25, 89–96 (2002).

    Article  CAS  Google Scholar 

  5. Lee, K. J., Dietrich, P. & Jessell, T. M. Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403, 734–740 (2000).

    Article  CAS  Google Scholar 

  6. Millonig, J. H., Millen, K. J. & Hatten, M. E. The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Nature 403, 764–769 (2000).

    Article  CAS  Google Scholar 

  7. Liem, K. F., Tremml, G. & Jessell, T. M. A role for the roof plate and its resident TGFβ-related proteins in neuronal patterning in the dorsal spinal cord. Cell 91, 127–138 (1997).

    Article  CAS  Google Scholar 

  8. Lee, K. J., Mendelsohn, M. & Jessell, T. M. 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 (1998).

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Muroyama, Y., Fujihara, M., Ikeya, M., Kondoh, H. & Takada, S. Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev. 16, 548–553 (2002).

    Article  CAS  Google Scholar 

  11. Chizhikov, V. V. & Millen, K. J. Control of roof plate formation by Lmx1a in the developing spinal cord. Development 131, 2693–2705 (2004).

    Article  CAS  Google Scholar 

  12. Chizhikov, V. V. & Millen, K. J. Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. J. Neurosci. 24, 5694–5703 (2004).

    Article  CAS  Google Scholar 

  13. Liu, Y., Helms, A. W. & Johnson, J. E. Distinct activities of Msx1 and Msx3 in dorsal neural tube development. Development 131, 1017–1028 (2004).

    Article  CAS  Google Scholar 

  14. Megason, S. G. & McMahon, A. P. A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129, 2087–2098 (2002).

    CAS  PubMed  Google Scholar 

  15. Millen, K. J., Millonig, J. H. & Hatten, M. E. Roof plate and dorsal spinal cord dl1 interneuron development in the dreher mutant mouse. Dev. Biol. 270, 382–392 (2004).

    Article  CAS  Google Scholar 

  16. Augsburger, A., Schuchardt, A., Hoskins, S., Dodd, J. & Butler, S. BMPs as mediators of roof plate repulsion of commissural neurons. Neuron 24, 127–141 (1999).

    Article  CAS  Google Scholar 

  17. Butler, S. J. & Dodd, J. A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons. Neuron 38, 389–401 (2003).

    Article  CAS  Google Scholar 

  18. Kahane, N. & Kalcheim, C. Identification of early postmitotic cells in distinct embryonic sites and their possible roles in morphogenesis. Cell Tissue Res. 294, 297–307 (1998).

    Article  CAS  Google Scholar 

  19. Luo, G. et al. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev. 9, 2808–2820 (1995).

    Article  CAS  Google Scholar 

  20. Dudley, A. T., Lyons, K. M. & Robertson, E. J. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev. 9, 2795–2807 (1995).

    Article  CAS  Google Scholar 

  21. Zhang, H. & Bradley, A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122, 2977–2986 (1996).

    CAS  Google Scholar 

  22. Winnier, G., Blessing, M., Labosky, P. A. & Hogan, B. L. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9, 2105–2116 (1995).

    Article  CAS  Google Scholar 

  23. Hollyday, M., McMahon, J. A. & McMahon, A. P. Wnt expression patterns in chick embryo nervous system. Mech. Dev. 52, 9–25 (1995).

    Article  CAS  Google Scholar 

  24. Garcia-Castro, M. I., Marcelle, C. & Bronner-Fraser, M. Ectodermal Wnt function as a neural crest inducer. Science 297, 848–851 (2002).

    CAS  Google Scholar 

  25. Wu, J., Saint-Jeannet, J. P. & Klein, P. S. Wnt-frizzled signaling in neural crest formation. Trends Neurosci. 26, 40–45 (2003).

    Article  CAS  Google Scholar 

  26. Wilson, L., Gale, E., Chambers, D. & Maden, M. Retinoic acid and the control of dorsoventral patterning in the avian spinal cord. Dev. Biol. 269, 433–446 (2004).

    Article  CAS  Google Scholar 

  27. Failli, V., Bachy, I. & Retaux, S. Expression of the LIM-homeodomain gene Lmx1a (dreher) during development of the mouse nervous system. Mech. Dev. 118, 225–228 (2002).

    Article  CAS  Google Scholar 

  28. Hill, R. E. et al. A new family of mouse homeo box-containing genes: molecular structure, chromosomal location, and developmental expression of Hox-7.1. Genes Dev. 3, 26–37 (1989).

    Article  CAS  Google Scholar 

  29. Robert, B., Sassoon, D., Jacq, B., Gehring, W. & Buckingham, M. Hox-7, a mouse homeobox gene with a novel pattern of expression during embryogenesis. EMBO J. 8, 91–100 (1989).

    Article  CAS  Google Scholar 

  30. Shimeld, S. M., McKay, I. J. & Sharpe, P. T. The murine homeobox gene Msx-3 shows highly restricted expression in the developing neural tube. Mech. Dev. 55, 201–210 (1996).

    Article  CAS  Google Scholar 

  31. Wang, W., Chen, X., Xu, H. & Lufkin, T. Msx3: a novel murine homologue of the Drosophila msh homeobox gene restricted to the dorsal embryonic central nervous system. Mech. Dev. 58, 203–215 (1996).

    Article  CAS  Google Scholar 

  32. Bronner-Fraser, M. & Fraser, S. E. Cell lineage analysis reveals multipotency of some avian neural crest cells. Nature 335, 161–164 (1988).

    Article  CAS  Google Scholar 

  33. Bronner-Fraser, M. & Fraser S. Developmental potential of avian trunk neural crest cells in situ. Neuron 3, 755–766 (1989).

    Article  CAS  Google Scholar 

  34. Selleck, M. A. and Bronner-Fraser, M. Origins of the avian neural crest: the role of neural plate-epidermal interactions. Development 121, 525–538 (1995).

    CAS  PubMed  Google Scholar 

  35. Knecht, A. K. & Bronner-Fraser, M. Induction of the neural crest: a multigene process. Nature Rev. Genet. 3, 453–461 (2002).

    Article  CAS  Google Scholar 

  36. Helms, A. W. & Johnson, J. E. Progenitors of dorsal commissural interneurons are defined by MATH1 expression. Development 125, 919–928 (1998).

    CAS  PubMed  Google Scholar 

  37. Manzanares, M., Trainor, P. A., Ariza-McNaughton, L., Nonchev, S. & Krumlauf, R. Dorsal patterning defects in the hindbrain, roof plate and skeleton in the dreher (dr(J)) mouse mutant. Mech. Dev. 94, 147–156 (2000).

    Article  CAS  Google Scholar 

  38. Nieto, M. A., Sargent, M. G., Wilkinson, D. G. & Cooke, J. Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 264, 835–839 (1994).

    Article  CAS  Google Scholar 

  39. Liu, J. P. & Jessell, T. M. A role for rhoB in the delamination of neural crest cells from the dorsal neural tube. Development 125, 5055–5067 (1998).

    CAS  PubMed  Google Scholar 

  40. Kos, R., Reedy, M. V., Johnson, R. L. & Erickson, C. A. The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos. Development 128, 1467–1479 (2001).

    CAS  PubMed  Google Scholar 

  41. Dottori, M., Gross, M. K., Labosky, P. & Goulding, M. The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate. Development 128, 4127–4138 (2001).

    CAS  PubMed  Google Scholar 

  42. Gammill, L. S. & Bronner-Fraser, M. Genomic analysis of neural crest induction. Development 129, 5731–5741 (2002).

    Article  CAS  Google Scholar 

  43. Muller, T. et al. The homeodomain factor lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord. Neuron 34, 551–562 (2002).

    Article  CAS  Google Scholar 

  44. Gross, M. K., Dottori, M. & Goulding, M. Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron 34, 535–549 (2002).

    Article  CAS  Google Scholar 

  45. Caspary, T. & Anderson, K. V. Patterning cell types in the dorsal spinal cord: what the mouse mutants say. Nature Rev. Neurosci. 4, 289–297 (2003).

    Article  Google Scholar 

  46. Helms, A. W. & Johnson, J. E. Specification of dorsal spinal cord interneurons. Curr. Opin. Neurobiol. 13, 42–49 (2003).

    Article  CAS  Google Scholar 

  47. Bergstrom, D. E., Gagnon, L. H. & Eicher, E. M. Genetic and physical mapping of the dreher locus on mouse chromosome 1. Genomics 59, 291–299 (1999).

    Article  CAS  Google Scholar 

  48. Sekiguchi, M., Shimai, K., Guo, H. & Nowakowski, R. S. Cytoarchitectonic abnormalities in hippocampal formation and cerebellum of dreher mutant mouse. Brain Res. Dev. Brain Res. 67, 105–112 (1992).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to A. Lindgren, I. Grinberg, C. Logan and E. Steshina for helpful discussion of the manuscript. This work was supported by grants from the Brain Research Foundation and the Whitehall Foundation.

Author information

Authors and Affiliations

  1. the Department of Human Genetics, University of Chicago, 920 East 58th Street, CLSC 319, Chicago, 60637, Illinois, USA

    Victor V. Chizhikov & Kathleen J. Millen

Authors
  1. Victor V. Chizhikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen J. Millen
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez Gene

BMP4

BMP7

follistatin

LHX2

Lmx1a

MATH1

noggin

RHOB

WNT1

FURTHER INFORMATION

Millen's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chizhikov, V., Millen, K. Mechanisms of roof plate formation in the vertebrate CNS. Nat Rev Neurosci 5, 808–812 (2004). https://doi.org/10.1038/nrn1520

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn1520

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing