The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance.
Developing axons are guided to their targets by attractive and repulsive guidance cues. In the embryonic spinal cord, the floor plate chemoattractant Netrin-1 is required to guide commissural neuron axons to the midline. However, genetic evidence suggests that other chemoattractant(s) are also involved. We show that the morphogen Sonic hedgehog (Shh) can mimic the additional chemoattractant activity of the floor plate in vitro and can act directly as a chemoattractant on isolated axons. Cyclopamine-mediated inhibition of the Shh signaling mediator Smoothened (Smo) or conditional inactivation of Smo in commissural neurons indicate that Smo activity is important for the additional chemoattractant activity of the floor plate in vitro and for the normal projection of commissural axons to the floor plate in vivo. These results provide evidence that Shh, acting via Smo, is a midline-derived chemoattractant for commissural axons and show that a morphogen can also act as an axonal chemoattractant.
Charron
Frédéric
F
Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Stein
Elke
E
Jeong
Juhee
J
McMahon
Andrew P
AP
Tessier-Lavigne
Marc
M
D000818:Animals; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002633:Chemotaxis / Q000235:genetics*; D058969:Contactin 2; D005333:Fetus; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D053823:Hedgehog Proteins; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics; D000075388:Netrin-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism / Q000637:transplantation; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014704:Veratrum Alkaloids / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D014982:Xenopus laevis; D029961:Zebrafish Proteins
D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D053823:Hedgehog Proteins; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D014704:Veratrum Alkaloids; D014764:Viral Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C491021:smo protein, zebrafish; D000075388:Netrin-1; C045073:Cre recombinase; D019426:Integrases; C000541:cyclopamine