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The Journal of Neuroscience, February 1, 2000, 20(3):1030-1035

Spatial Distributions of Guidance Molecules Regulate Chemorepulsion and Chemoattraction of Growth Cones

Dominique Bagnard¹, Nicole Thomasset², Marion Lohrum³, Andreas W. Püschel³, and Jürgen Bolz⁴

¹ Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 371, Cerveau et Vision, 69500 Bron, France, ² INSERM Unité 433, Faculté de Médecine Laennec, 69372 Lyon cedex 08, France, ³ Max-Planck-Institut für Hirnforschung, Molekulare Neurogenetik, Abt. Neurochemie, 60528 Frankfurt, Germany, and ⁴ Universität Jena, Institut für Allgemeine Zoologie, 07743 Jena, Germany

It is generally assumed that gradients of chemotropic molecules are instrumental to the wiring of the nervous system. Recently, two members of the secreted class III semaphorin protein family have been implicated as repulsive (Sema3A) and attractive (Sema3C) guidance molecules for cortical axons (Bagnard et al., 1998). Here, we show that stabilized gradients of increasing semaphorin concentrations elicit stereotyped responses from cortical growth cones, independent of the absolute concentration and the slope of these gradients. In contrast, neither repulsive effects of Sema3A nor attractive effects of Sema3C were observed when axons were growing toward decreasing semaphorin concentrations. Thus, growth cone guidance by gradients of chemotropic molecules is robust and reproducible, because it is primarily independent of the exact dimensions of the gradients.

Key words: wiring molecules; axonal guidance; gradients; chemotropic attraction; chemotropic repulsion; semaphorins; cortical development; in vitro assays; time-lapse imaging

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2031030-06$05.00/0

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