Bmp and Wnt/beta-catenin Signals Control Expression of the Transcription Factor Olig3 and the Specification of Spinal Cord Neurons

Dev Biol. 2007 Mar 1;303(1):181-90. doi: 10.1016/j.ydbio.2006.10.045. Epub 2006 Nov 6.

Abstract

In the developing spinal cord, signals of the roof plate pattern the dorsal progenitor domain and control the specification of three neuron types, dorsal interneurons dI1, dI2, and dI3. Bmp and Wnt/beta-catenin signals as well as transcription factors like Olig3 or Ngn1/2 are essential in this process. We have studied the epistatic relationship between Bmp and Wnt/beta-catenin signals and the transcription factor Olig3 in dorsal spinal cord patterning. Using beta-catenin gain-of-function and compound beta-catenin gain-of-function/Olig3 loss-of-function mutations in mice, we could show that Wnt/beta-catenin signals act upstream of Olig3 in the specification of dI2 and dI3 neurons. The analysis of such compound mutant mice allowed us to distinguish between the two functions of Wnt/beta-catenin signaling in proliferation and patterning of dorsal progenitors. Using electroporation of chick spinal cords, we further demonstrate that Bmp signals act upstream of Wnt/beta-catenin in the regulation of Olig3 and that Wnt/beta-catenin signals play an instructive role in controlling Olig3 expression. We conclude that Wnt/beta-catenin and BMP signals coordinately control the specification of dorsal neurons in the spinal cord.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation / physiology*
  • Chick Embryo
  • Electroporation
  • Epistasis, Genetic
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental*
  • In Situ Hybridization
  • Mice
  • Morphogenesis / physiology*
  • Mutation / genetics
  • Neurons / cytology*
  • Signal Transduction / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Wnt Proteins / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Bone Morphogenetic Proteins
  • Olig3 protein, mouse
  • Wnt Proteins
  • beta Catenin