Semaphorin Signaling

Recent advances in our understanding of axon guidance during neural development are highlighted by the characterization of several gene families containing members capable of functioning as repellents. These include ephrins, netrins, and semaphorins. Though future work will undoubtedly result in the identification of still more repellents, the wealth of information now in hand concerning the cellular and molecular basis of repulsive guidance demands that we turn our attention toward how these repulsive cues actually direct discrete steering events. Pharmacological experiments are beginning to provide important insights into the basis of repulsive guidance signaling mechanisms in cell culture (Song et al. 1998). However, the characterization of endogenous receptors through which these cues transduce extracellular signals is paramount to addressing this issue in vivo. The knowledge that Eph receptor tyrosine kinases (RTKs) function as ephrin receptors and that UNC40 and UNC5 gene family members function as netrin receptors provides important clues for characterizing the intracellular signaling pathways activated by these guidance cues. The identification of semaphorin receptors, however, is only now beginning to point the way toward elucidating the signaling pathways used by semaphorins during neural development to direct extending growth cones away from inappropriate targets.