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

Dev Biol. 2007 Apr 1;304(1):394-408. doi: 10.1016/j.ydbio.2006.12.045. Epub 2006 Dec 23.

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 beta-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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Morphogenetic Proteins / metabolism*
  • Bromodeoxyuridine
  • Cell Differentiation / physiology*
  • Cell Proliferation*
  • Galactosides
  • Indoles
  • Mice
  • Microscopy, Fluorescence
  • Models, Biological
  • Neuroepithelial Cells / metabolism
  • Neuroepithelial Cells / physiology*
  • Signal Transduction / physiology*
  • Spinal Cord / embryology*
  • Wnt Proteins / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Galactosides
  • Indoles
  • Wnt Proteins
  • Bromodeoxyuridine
  • 5-bromo-4-chloro-3-indolyl beta-galactoside