Sema4d is required for the development of the hindbrain boundary and skeletal muscle in zebrafish

Semaphorin4d (SEMA4D), also known as CD100, an oligodendrocyte secreted R-Ras GTPase-activating protein (GAP), affecting axonal growth is involved in a range of processes including cell adhesion, motility, angiogenesis, immune responses and tumour progression. However, its actual physiological mechanisms and its role in development remain unclear. This study has focused on the role of sema4d in the development and expression patterns in zebrafish embryos and the effect of its suppression on development using sema4d-specific antisense morpholino-oligonucleotides. In this study the knockdown of sema4d, expressed at all developmental stages, lead to defects in the hindbrain and trunk structure of zebrafish embryos. In addition, these phenotypes appeared to be associated with the abnormal expression of three hindbrain rhombomere boundary markers, wnt1, epha4a and foxb1.2, and two myogenic regulatory factors, myod and myog. Further, a notable increase of cell apoptosis appeared in the sema4d knockdown embryos, while no obvious reduction in cell proliferation was observed. Collectively, these data suggest that sema4d plays an important role in the development of the hindbrain and skeletal muscle.

► Sema4d was expressed at all developmental stages of zebrafish.
► Knockdown of sema4d in embryos resulted in defects in the hindbrain and the trunk structure.
► Knockdown of sema4d in embryos upregulated the expression of three hindbrain rhombomere markers.
► Knockdown of sema4d in embryos increased the expression of myogenic regulatory factors.
► Knockdown of sema4d in embryos resulted in an obvious increase of cell apoptosis.