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Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling.

Publication ,  Journal Article
Ybot-Gonzalez, P; Gaston-Massuet, C; Girdler, G; Klingensmith, J; Arkell, R; Greene, NDE; Copp, AJ
Published in: Development
September 2007

Dorsolateral bending of the neural plate, an undifferentiated pseudostratified epithelium, is essential for neural tube closure in the mouse spinal region. If dorsolateral bending fails, spina bifida results. In the present study, we investigated the molecular signals that regulate the formation of dorsolateral hinge points (DLHPs). We show that Bmp2 expression correlates with upper spinal neurulation (in which DLHPs are absent); that Bmp2-null embryos exhibit premature, exaggerated DLHPs; and that the local release of Bmp2 inhibits neural fold bending. Therefore, Bmp signalling is necessary and sufficient to inhibit DLHPs. By contrast, the Bmp antagonist noggin is expressed dorsally in neural folds containing DLHPs, noggin-null embryos show markedly reduced dorsolateral bending and local release of noggin stimulates bending. Hence, Bmp antagonism is both necessary and sufficient to induce dorsolateral bending. The local release of Shh suppresses dorsal noggin expression, explaining the absence of DLHPs at high spinal levels, where notochordal expression of Shh is strong. DLHPs ;break through' at low spinal levels, where Shh expression is weaker. Zic2 mutant embryos fail to express Bmp antagonists dorsally and lack DLHPs, developing severe spina bifida. Our findings reveal a molecular mechanism based on antagonism of Bmp signalling that underlies the regulation of DLHP formation during mouse spinal neural tube closure.

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Published In

Development

DOI

ISSN

0950-1991

Publication Date

September 2007

Volume

134

Issue

17

Start / End Page

3203 / 3211

Location

England

Related Subject Headings

  • Transforming Growth Factor beta
  • Transcription Factors
  • Spinal Dysraphism
  • Signal Transduction
  • Notochord
  • Nervous System
  • Morphogenesis
  • Models, Biological
  • Mice, Transgenic
  • Mice, Inbred Strains
 

Citation

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Ybot-Gonzalez, P., Gaston-Massuet, C., Girdler, G., Klingensmith, J., Arkell, R., Greene, N. D. E., & Copp, A. J. (2007). Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. Development, 134(17), 3203–3211. https://doi.org/10.1242/dev.008177
Ybot-Gonzalez, Patricia, Carles Gaston-Massuet, Gemma Girdler, John Klingensmith, Ruth Arkell, Nicholas D. E. Greene, and Andrew J. Copp. “Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling.Development 134, no. 17 (September 2007): 3203–11. https://doi.org/10.1242/dev.008177.
Ybot-Gonzalez P, Gaston-Massuet C, Girdler G, Klingensmith J, Arkell R, Greene NDE, et al. Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. Development. 2007 Sep;134(17):3203–11.
Ybot-Gonzalez, Patricia, et al. “Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling.Development, vol. 134, no. 17, Sept. 2007, pp. 3203–11. Pubmed, doi:10.1242/dev.008177.
Ybot-Gonzalez P, Gaston-Massuet C, Girdler G, Klingensmith J, Arkell R, Greene NDE, Copp AJ. Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. Development. 2007 Sep;134(17):3203–3211.
Journal cover image

Published In

Development

DOI

ISSN

0950-1991

Publication Date

September 2007

Volume

134

Issue

17

Start / End Page

3203 / 3211

Location

England

Related Subject Headings

  • Transforming Growth Factor beta
  • Transcription Factors
  • Spinal Dysraphism
  • Signal Transduction
  • Notochord
  • Nervous System
  • Morphogenesis
  • Models, Biological
  • Mice, Transgenic
  • Mice, Inbred Strains