Functional analysis of zebrafish Semaphorin4E.

Abstract

The network of connections between neurons in the nervous system is both highly complicated and specific. How these connections are made is one of the fundamental questions in neuroscience. The basis of the accuracy is maintained by molecules that serve to attract, repulse, and identify pathways for growth cones. Semaphorins are one of the several families of related proteins involved in axon guidance. The semaphorins gene family is a large and diverse family enoding both secreted and cell membrane bound proteins. I am studying the function of the zebrafish class 4 Semaphorin4E (Sema4E). Sema4E is expressed in specific regions of the embryo that suggest Sema4E guides a variety of growth cones, including those of spinal cord neurons, branchiomotor neurons in the hindbrain, and the retinal neurons, to their targets. By using molecular, cellular and genetic techniques, I identified several potential functions of Sema4E: Sema4E repulses branchiomotor axons and restricts them within the boundary of each pharyngeal arch, Sema4E regulates DLF fasciculation in the spinal cord, Sema4E binds sensory neurons and inhibits their growth cones in vitro, and Sema4E induces primary motor axons branching. Furthermore, the characterization of zebrafish PlexinA2 suggests that it is a candidate receptor for Sema4E.