Spatial distributions of guidance molecules regulate chemorepulsion and chemoattraction of growth cones

It is generally assumed that gradients of chemotropic molecules are instrum ental to the wiring of the nervous system. Recently, two members of the sec reted class III semaphorin protein family have been implicated as repulsive (Sema3A) and attractive (Sema3C) guidance molecules for cortical axons (Ba gnard 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 gr adients. In contrast, neither repulsive effects of Sema3A nor attractive ef fects of Sema3C were observed when axons were growing toward decreasing sem aphorin concentrations. Thus, growth cone guidance by gradients of chemotro pic molecules is robust and reproducible, because it is primarily independe nt of the exact dimensions of the gradients.