Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord

Fabian Ille, Suzana Atanasoski, Sven Falk, Lars M. Ittner, David Märki, Stine Büchmann-Møller, Heiko Wurdak, Ueli Suter, Makoto M. Taketo, Lukas Sommer*

*Corresponding author for this work

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Multiple signaling pathways regulate proliferation and differentiation of neural progenitor cells during early development of the central nervous system (CNS). In the spinal cord, dorsal signaling by bone morphogenic protein (BMP) acts primarily as a patterning signal, while canonical Wnt signaling promotes cell cycle progression in stem and progenitor cells. However, overexpression of Wnt factors or, as shown here, stabilization of the Wnt signaling component β-catenin has a more prominent effect in the ventral than in the dorsal spinal cord, revealing local differences in signal interpretation. Intriguingly, Wnt signaling is associated with BMP signal activation in the dorsal spinal cord. This points to a spatially restricted interaction between these pathways. Indeed, BMP counteracts proliferation promoted by Wnt in spinal cord neuroepithelial cells. Conversely, Wnt antagonizes BMP-dependent neuronal differentiation. Thus, a mutually inhibitory crosstalk between Wnt and BMP signaling controls the balance between proliferation and differentiation. A model emerges in which dorsal Wnt/BMP signal integration links growth and patterning, thereby maintaining undifferentiated and slow-cycling neural progenitors that form the dorsal confines of the developing spinal cord.

Original languageEnglish
Pages (from-to)394-408
Number of pages15
JournalDevelopmental Biology
Volume304
Issue number1
DOIs
Publication statusPublished - 1 Apr 2007
Externally publishedYes

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Keywords

  • BMP
  • Differentiation
  • Neuroepithelial stem cell
  • Proliferation
  • Spinal cord development
  • Wnt
  • β-catenin

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