Chapter 11 Semaphorin-mediated neuronal growth cone guidance

Abstract

The semaphorin family contains a large number of phylogenetically conserved proteins and includes several members that have been shown to function in repulsive axon guidance. The importance of repulsive cues in path finding and target selection has now been firmly established at the cellular and molecular levels. Semaphorin III (Sema III) is a secreted protein that in vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and in vivo is required for correct sensory afferent innervations and other aspects of development. The mechanism of Sema III function, however, is unknown. This chapter reviews experiments demonstrating that neuropilin- 1, a type I transmembrane protein implicated in aspects of neurodevelopment, is a Sema III receptor or component of a receptor complex. Neuropilin-1 is the founding member of a gene family, including neuropilin-2, a related protein that is expressed in overlapping, yet distinct, populations of neurons in rat embryonic nervous system. These experiments suggest that the neuropilins play a critical role in imparting specificity to the action of semaphorins during neurodevelopment. In addition, evidence is accumulating that transmembrane semaphorins also play essential roles in peripheral and CNS axon guidance events. Drosophila semaphorin I (D-Sema I) is a transmembrane protein that in vivo is required for motor and central nervous system (CNS) axon guidance events. Genetic experiments in Drosophila strongly suggest that D-Sema I also can function as a repulsive guidance cue.