Many Major CNS Axon Projections Develop Normally in the Absence of Semaphorin III

Abstract

The semaphorins constitute a large gene family of transmembrane and secreted molecules, many of which are expressed in the nervous system. Genetic studies inDrosophilahave revealed a role for semaphorins in axon guidance and synapse formation, and severalin vitrostudies in mice have demonstrated a dramatic chemorepellent effect of semaphorin III (Sema III) on the axons of several populations of neurons. To investigate the function of Sema III duringin vivoaxon guidance in the mammalian CNS, we studied the development of axonal projections in mutant mice lacking Sema III. Projections were studied for which either thein vitroevidence suggests a role for Sema III in axon guidance (e.g., cerebellar mossy fibers, thalamocortical axons, or cranial motor neurons) or thein vivoexpression suggests a role for Sema III in axon guidance (e.g., cerebellar Purkinje cells, neocortex). We find that many major axonal projections, including climbing fiber, mossy fiber, thalamocortical, and basal forebrain projections and cranial nerves, develop normally in the absence of Sema III. Despite itsin vitrofunction andin vivoexpression, it appears as if Sema III is not absolutely required for the formation of many major CNS tracts. Such data are consistent with recent models suggesting that axon guidance is controlled by a balance of forces resulting from multiple guidance cues. Our data lead us to suggest that if Sema III functions in part to guide the formation of major axonal projections, then it does so in combination with both other semaphorins and other families of guidance molecules.