Semaphorins are a family of secreted and membrane-bound proteins, known to control axonal pathfinding. It was recently demonstrated that Semaphorin 4A (Sema4A) is crucially involved in immune cell activation. However, the role of Sema4A in the nervous system has not yet been clarified. To examine if Sema4A can function as a chemo-repulsive cue to growth cones of developing hippocampal neurons, a growth cone collapse assay with recombinant Sema4A was performed in primary hippocampal neurons cultured from E17 mice. In these primary hippocampal neurons, Sema4A induced a significant growth cone collapse as compared with the culture without Sema4A. The Sema4A-induced growth cone collapse could be blocked by Y-27632, a Rho-kinase inhibitor. Furthermore, immunocytochemical analysis with antibodies against Sema4A demonstrated the binding of recombinant Sema4A to the growth cones of hippocampal neurons. Thus, our data indicated that Sema4A could function as a chemo-repulsive cue by activating a receptor whose signal is transmitted to Rho-kinase and induced growth cone collapse of hippocampal neurons.

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