TY - JOUR
T1 - The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with Netrin-1 in midline axon guidance
AU - Charron, Frédéric
AU - Stein, Elke
AU - Jeong, Juhee
AU - McMahon, Andrew P.
AU - Tessier-Lavigne, Marc
N1 - Funding Information:
We thank A. Yaron, C. Sabatier, F. Wang, H. Long, J. Hao, K. Mitchell, L. Goodrich, M. Huse, O. Marin, R. Friedel and X. Lu and other members of the Tessier-Lavigne lab for helpful discussions and for sharing expertise and reagents; H. Lin, H. Rayburn, and S. Faynboym for technical assistance; P. Soriano and G. Barsh for providing the R26R mice, C.C. Hui for providing the Gli2 mutant mice; W. Gaffield for providing cyclopamine; and the Developmental Studies Hybridoma Bank for providing antibodies. This work was initiated while F.C. was a Human Frontier Science Program Fellow and continued as an Arnold and Mabel Beckman Foundation Senior Research Fellow. Work in A.P.M.'s laboratory was supported by a grant from the NIH (NS 33642). E.S. was an Associate and M.T.L. is an Investigator of the Howard Hughes Medical Institute.
PY - 2003/4/4
Y1 - 2003/4/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(03)00199-5
DO - 10.1016/S0092-8674(03)00199-5
M3 - Article
C2 - 12679031
AN - SCOPUS:0037418830
VL - 113
SP - 11
EP - 23
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -