A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons

Neuron. 2003 May 8;38(3):389-401. doi: 10.1016/s0896-6273(03)00254-x.

Abstract

During spinal cord development, commissural neurons extend their axons ventrally, away from the roof plate. The roof plate is the source of a diffusible repellent that orients commissural axons in vitro and, thus, may regulate the trajectory of commissural axons in vivo. Of three Bmps expressed in the roof plate, BMP7, but not BMP6 or GDF7, mimics the roof plate activity in vitro. We show here that expression of both Bmp7 and Gdf7 by roof plate cells is required for the fidelity of commissural axon growth in vivo. We also demonstrate that BMP7 and GDF7 heterodimerize in vitro and that, under these conditions, GDF7 enhances the axon-orienting activity of BMP7. Our findings suggest that a GDF7:BMP7 heterodimer functions as a roof plate-derived repellent that establishes the initial ventral trajectory of commissural axons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Body Patterning / genetics
  • Bone Morphogenetic Proteins / deficiency*
  • Bone Morphogenetic Proteins / genetics
  • COS Cells
  • Cell Communication / genetics
  • Cell Differentiation / genetics
  • Chemotaxis / genetics
  • Dimerization
  • Fetus
  • Functional Laterality / genetics
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Growth Differentiation Factors
  • Homeodomain Proteins / genetics
  • Immunohistochemistry
  • MSX1 Transcription Factor
  • Macromolecular Substances
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Spinal Cord / metabolism*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Bone Morphogenetic Proteins
  • Gdf7 protein, mouse
  • Growth Differentiation Factors
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • Macromolecular Substances
  • Transcription Factors
  • growth differentiation factor 7