Axon guidance by diffusible chemoattractants: a gradient of netrin protein in the developing spinal cord.
Gradients of diffusible long-range attractant and repellent proteins have been proposed to guide growing axons during nervous system development, but such gradients have never been visualized directly. In the embryonic spinal cord, commissural axons pioneer a circumferential trajectory to the floor plate at the ventral midline directed by secreted proteins of the netrin family. In the embryonic chick spinal cord netrin-1 mRNA is expressed by floor plate cells and netrin-2 mRNA by neural epithelial cells. Antibodies to the two netrins reveal a gradient of netrin protein directly in the path of commissural axons. The netrin-1 gradient itself extends many cell diameters dorsal to the floor plate, the site of netrin-1 expression. A similar distribution of netrin-1 protein has been detected in embryonic rat and mouse spinal cord. The detection of a gradient of netrin-1 protein supports the operation of long-range chemotropic mechanisms in the developing nervous system.
Kennedy
Timothy E
TE
Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143, USA.
Wang
Hao
H
Marshall
Wallace
W
Tessier-Lavigne
Marc
M
D000818:Animals; D001369:Axons / Q000502:physiology*; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology; D047108:Embryonic Development; D020439:Growth Cones / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D000075388:Netrin-1; D000075385:Netrins; D051381:Rats; D013116:Spinal Cord / Q000196:embryology*; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D002630:Chemotactic Factors; D009414:Nerve Growth Factors; D000075385:Netrins; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C088894:netrin-2