The semaphorin/collapsin gene family is a large and diverse family encoding both secreted and transmembrane proteins, some of which are thought to act as repulsive axon guidance molecules. However, the function of most semaphorins is still unknown. We have cloned and characterized several semaphorins in the zebrafish in order to assess their in vivo function. Zebrafish semaZ2 is expressed in a dynamic and restricted pattern during the period of axon outgrowth that indicates potential roles in the guidance of several axon pathways. Analysis of mutant zebrafish with reduced semaZ2 expression reveals axon pathfinding errors that implicate SemaZ2 in normal guidance.

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The large, conserved semaphorin/collapsin gene family encodes putative axon guidance molecules. We describe the cloning and expression of two n ovel zebrafish semaphorins that represent an increase in the size and diversity of the family. These semaphorins are expressed in unique and dynamic patterns during development.

The semaphorin/collapsin gene family encodes secreted and transmembrane proteins several of which can repulse growth cones. Although the in vitro activity of Semaphorin III/D/Collapsin 1 is clear, recent analyses of two different strains of semaphorin III/D/collapsin 1 knockout mice have generated conflicting findings. In order to clarify the in vivo action of this molecule, we analyzed sema Z1a, a zebrafish homolog of semaphorin III/D/collapsin 1. The expression pattern of sema Z1a suggested that it delimited the pathway of the growth cones of a specific set of sensory neurons, the posterior ganglion of the lateral line, in zebrafish. To examine the in vivo action of this molecule, we analyzed (1) the pathways followed by lateral line growth cones in mutants in which the expression of sema Z1a is altered in an interesting way, (2) response of lateral line growth cones to exogenous Sema Z1a in living embryos, and (3) the pathway followed by lateral line growth cones when Sema Z1a is misexpressed by cells along their normal route. The results suggest that a repulsive action of Sema Z1a helps guide the growth cones of the lateral line along their normal pathway.