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Science 302 (5652): 1984-1988

Copyright © 2003 by the American Association for the Advancement of Science

Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling

Anna I. Lyuksyutova,2 Chin-Chun Lu,1 Nancy Milanesio,1 Leslie A. King,2 Nini Guo,4 Yanshu Wang,4 Jeremy Nathans,4 Marc Tessier-Lavigne,5* Yimin Zou1,2,3{dagger}

Abstract: Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord.

1 Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA.
2 Committee on Developmental Biology, University of Chicago, Chicago, IL 60637, USA.
3 Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
4 Departments of Molecular Biology and Ophthalmology, Howard Hughes Medical Institute, Johns Hopkins Medical School, Baltimore, MD 21205, USA.
5 Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA94305, USA.

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* Present address: Genentech Inc., South San Francisco, CA94080, USA.

{dagger} To whom correspondence should be addressed. E-mail: yzou{at}bsd.uchicago.edu

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