A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons.
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.
Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Samantha J
SJ
Butler
Jane
J
Dodd
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000172:deficiency* / Q000235:genetics; D019556:COS Cells; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002633:Chemotaxis / Q000235:genetics; D019281:Dimerization; D005333:Fetus; D007839:Functional Laterality / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D051957:MSX1 Transcription Factor; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D046911:Macromolecular Substances; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C499471:Gdf7 protein, mouse; C086559:growth differentiation factor 7