Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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COS Cells
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Cell Adhesion Molecules, Neuronal / genetics
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Communication / genetics
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Cell Differentiation / genetics*
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Chemotaxis / genetics*
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Contactin 2
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Fetus
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Hedgehog Proteins
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Integrases / genetics
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Integrases / metabolism
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Mice
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Mice, Mutant Strains
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Nerve Growth Factors / deficiency*
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Nerve Growth Factors / genetics
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Netrin-1
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Rats
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled*
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Smoothened Receptor
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Spinal Cord / embryology*
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Spinal Cord / metabolism
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Spinal Cord / transplantation
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Trans-Activators / metabolism*
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Tumor Suppressor Proteins
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Veratrum Alkaloids / pharmacology
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Viral Proteins / genetics
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Viral Proteins / metabolism
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Wnt Proteins
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Xenopus laevis
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Zebrafish Proteins*
Substances
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Cell Adhesion Molecules, Neuronal
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Cntn2 protein, mouse
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Contactin 2
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Hedgehog Proteins
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Nerve Growth Factors
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Ntn1 protein, mouse
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Ntn1 protein, rat
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Smo protein, mouse
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Smoothened Receptor
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Trans-Activators
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Tumor Suppressor Proteins
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Veratrum Alkaloids
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Viral Proteins
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Wnt Proteins
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Zebrafish Proteins
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smo protein, zebrafish
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Netrin-1
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Cre recombinase
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Integrases
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cyclopamine