Role of Semaphorins in axonal guidance

信号蛋白在轴突引导中的作用

• 批准号: 6471379
• 负责人: JOHN Y KUWADA
• 金额: $ 35.38万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6471379
• 关键词: chemoattractants; developmental neurobiology; embryo /fetus; gene expression; genetically modified animals; growth cones; lasers; macromolecule; neurogenesis; neuronal guidance; protein structure function; recombinant proteins; zebrafish

DESCRIPTION (provided by applicant): Semaphorins are a large family of molecules that repulse growth cones, but in some cases also attract them. The analyses of semaphorins and their neuropilin/plexin receptors have made important advances in our understanding of how growth cones are guided to their targets. However, our understanding of the function of semaphorins is still incomplete. First, the functional analysis of vertebrate semaphorins has been mostly of the secreted, Class 3 semaphorins. Our understanding of the function of the large transmembrane, Class 4 semaphorins is limited to Sema4D/CD100which plays a vital role in the immune system, but no nervous system function is known for any Class 4 semaphorin. This application will examine how Sema4E, a novel Class 4 semaphorin recently cloned by our lab, guides growth cones in the zebrafish embryo. Second, most vertebrate semaphorins that affect neurons exhibit a repulsive effect on axons, although in certain circumstances semaphorins can attract growth cones in vitro. Nevertheless, there are no examples of attractive actions on axons by a vertebrate semaphorin in vivo. This application will examine whether Sema3D, whose function is unknown in any organism, attracts and/or induces branching by axons in vivo in zebrafish embryos. The accessibility, manipulability, and transparency of the embryo have led to high resolution, cellular analyses of how specific growth cones find their targets in zebrafish. Furthermore, our laboratory has generated transgenic zebrafish in which several semaphorins can be induced, shown that transgenes can be activated in individual cells by focusing a laser microbeam onto cells, "knocked down" semaphorins by injection of morpholino antisense oligos and applied dominant negative strategies. Preliminary evidence suggests that Sema4E and Sema3Al may restrict branchiomotor axons to their normal pathway, while Sema3D may attract or induce branching within the pharyngeal arch targets of these axons. This application will use these transgenic lines and generate new ones in order to assay both gain- and loss-of-function phenotypes for Sema4E, Sema3Al, and Sema3D to clarify their roles for guidance of the branchiomotor growth cones to and within the pharyngeal arches that they innervate.

描述（由申请人提供）：信号量是一个大家庭