Abstract
Semaphorins are a family of secreted and membrane-bound proteins, known to control axonal pathfinding. Semaphorin4A(Sema4A) has recently been shown to be involved in immune cell activation. However, the role of Sema4A in the nervous system is totally unknown. To examine if Sema4A functions as a chemo-repulsive cue to growth cones of developing hippocampal neurons, growth cone collapse assay with recombinant Sema4A was performed in primary hippocampal neurons cultured from E17 rats or mice. As a result, Sema4A induced a significant growth cone collapse in hippocampal neurons as compared with the culture without Sema4A. The Sema4A-induced growth cone collapse could be blocked by Y-27632, the Rho-kinase inhibitor. The neurite outgrowth assay suggested that Sema4A could work as a retraction inducer by inhibiting neurite outgrowth of hippocampal neurons. Furthermore, an immunocytochemical analysis using the antibodies to Sema4A directly 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 an unknown receptor whose signal is transmitted to Rho-kinase to induce growth cone collapse of hippocampal neurons. Consistent with the data above, our preliminary analyses of Sema4A knockout mice suggested that the infrapyramidal mossy fiber projection in the hippocampus was abnormally longer than that of wild-type mice. The overshooting phenotype implies that Sema4A can be a guidance cue controlling the proper formation of neuronal network in vivo. [Jpn J Physiol 54 Suppl:S213 (2004)]
