Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord.
The guidance of axons to their targets in the developing nervous system is believed to involve diffusible chemotropic factors secreted by target cells. Floor plate cells at the ventral midline of the spinal cord secrete a diffusible factor or factors that promotes the outgrowth of spinal commissural axons and attracts these axons in vitro. Two membrane-associated proteins isolated from brain, netrin-1 and netrin-2, possess commissural axon outgrowth-promoting activity. We show here that netrin-1 RNA is expressed by floor plate cells, whereas netrin-2 RNA is detected at lower levels in the ventral two-thirds of the spinal cord, but not the floor plate. Heterologous cells expressing recombinant netrin-1 or netrin-2 secrete diffusible forms of the proteins and can attract commissural axons at a distance. These results show that netrin-1 is a chemotropic factor expressed by floor plate cells and suggest that the two netrin proteins guide commissural axons in the developing spinal cord.
Kennedy
T E
TE
Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452.
Serafini
T
T
de la Torre
J R
JR
Tessier-Lavigne
M
M
D000818:Animals; D001369:Axons / Q000187:drug effects*; D002450:Cell Communication; D016764:Cell Polarity; D002478:Cells, Cultured; D004058:Diffusion; D009414:Nerve Growth Factors / Q000235:genetics / Q000494:pharmacology*; D009415:Nerve Net / Q000254:growth & development; D000075388:Netrin-1; D000075385:Netrins; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000254:growth & development*; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins
D009414:Nerve Growth Factors; D000075385:Netrins; C000617354:Ntn1 protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C088894:netrin-2