Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance.
During embryonic development, morphogens act as graded positional cues to dictate cell fate specification and tissue patterning. Recent findings indicate that morphogen gradients also serve to guide axonal pathfinding during development of the nervous system. These findings challenge our previous notions about morphogens and axon guidance molecules, and suggest that these proteins, rather than having sharply divergent functions, act more globally to provide graded positional information that can be interpreted by responding cells either to specify cell fate or to direct axonal pathfinding. This review presents the roles identified for members of three prominent morphogen families--the Hedgehog, Wnt and TGFbeta/BMP families--in axon guidance, and discusses potential implications for the molecular mechanisms underlying their guidance functions.
Charron
Frédéric
F
Department of Biological Sciences, Stanford University, 371 Serra Mall, Stanford, California 94305, USA.
Tessier-Lavigne
Marc
M
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D019521:Body Patterning / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001921:Brain / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology*; D020439:Growth Cones / Q000378:metabolism* / Q000502:physiology; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051153:Wnt Proteins
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D000075388:Netrin-1