During spinal cord development, commissural (C) neurons, located near the dorsal midline, send axons ventrally and across the floor plate (FP). The trajectory of these axons toward the FP is guided in part by netrins. The mechanisms that guide the early phase of C axon extension, however, have not been resolved. We show that the roof plate (RP) expresses a diffusible activity that repels C axons and orients their growth within the dorsal spinal cord. Bone morphogenetic proteins (BMPs) appear to act as RP-derived chemorepellents that guide the early trajectory of the axons of C neurons in the developing spinal cord: BMP7 mimics the RP repellent activity for C axons in vitro, can act directly to collapse C growth cones, and appears to serve an essential function in RP repulsion of C axons.
Bibliographical noteFunding Information:
We are grateful to R. Harland for noggin, K. Lee for chordin, J. Raper for collapsin cDNAs, M. Tessier-Lavigne for the netrin expression vector, J. Kitajewski for wnts, and E. Robertson for Bmp7 mutant mice. Antibodies were provided by J. Johnson (α-mATH-1), T. Jessell (α-LH2A/B, α-Isl 1, and α-SHH), M. Nishizawa (α-MafB), K. Sampath (α-BMP7), and F. Solomon (α-ezrin). We are indebted to J. Briscoe and S. Sockanathan for advice on confocal microscopy. We wish to thank L. Greene, T. Jessell, M. Placzek, and members of the Dodd and Jessell labs for helpful discussions and to J. Heemskerk, T. Jessell, K. Lee, and C. Mason for comments on the manuscript. The work was funded by a grant from the NIH, NS 27113, to J. D.