Sema3D Role in Retinal Axon Guidance and Cell Migration

Sema3D 在视网膜轴突引导和细胞迁移中的作用

• 批准号: 6544137
• 负责人: MARY C HALLORAN
• 金额: $ 27.23万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6544137
• 关键词: axon; cell growth regulation; cell migration; cell motility; developmental neurobiology; embryo /fetus; gene expression; genetically modified animals; glycoproteins; growth cones; neural crest; neuronal guidance; receptor expression; retina; transfection; video microscopy; zebrafish

DESCRIPTION (provided by applicant): Semaphorins have been implicated in the regulation of axon pathfinding, sometimes acting as inhibitory guidance molecules, and other times attractive. An understanding of the complex processes involved in promoting and inhibiting axon growth will be crucial for understanding both diseases of neural development, and the conditions under which axon regeneration after injury can occur. Semaphorins also are thought to play a role in controlling the related processes of cell migration during development, metastasis and invasive growth. Cranial neural crest cells migrate from the neural tube to form craniofacial structures and peripheral nervous system. Errors in migration of cranial neural crest during development underlies many birth defects in craniofacial structure. An investigation of the mechanisms by which semaphorins control neural crest migration will provide insight into craniofacial development, and perhaps also general mechanisms of invasive growth involved in cancer progression.The aim of this application is to understand the in vivo function of one semaphorin, Sema3D, in guiding retinotectal axon pathfinding and neural crest cell migration in the developing zebrafish. Sema3D's role in guiding retinal axons across the midline and in topographic mapping onto the tectum will be investigated. In addition, Sema3D's role in controlling cell motility will be investigated to test the hypotheses that Sema3D induces the onset of neural crest migration, and/or maintains separation of migrating neural crest streams. Our strategy is to examine effects of both Sema3D ectopic expression and Sema3D loss-of-function on the development of these systems, and on dynamic behaviors of living growth cones and migrating neural crest cells in vivo. The zebrafish embryo is ideally suited to the combination of approaches we have developed. With transgenic zebrafish, Sema3D can be misexpressed in select cells at any desired developmental stage. In addition, Sema3D function can be disrupted with antisense or dominant negative methods. Time-lapse microscopy allows direct visualization of the responses of living growth cones or migrating cells in the embryo. Thus the proposed experiments will likely provide novel insights into how semaphorins regulate retinal axon development and neural crest cell migration within the complex in vivo environment.

描述（由申请人提供）：信号素与轴突路径的调节有关，有时充当抑制性引导分子，而其他时间有吸引力。对促进和抑制轴突生长所涉及的复杂过程的理解对于理解神经发育的疾病以及受伤后轴突再生的条件至关重要。信号素还被认为在控制开发，转移和侵入性生长过程中的相关过程中发挥作用。颅神经rest细胞从神经管迁移，形成颅面结构和周围神经系统。发育过程中颅神经rest迁移的错误是颅面结构中许多先天缺陷的基础。对词素控制神经rest迁移的机制的研究将为颅面发展提供深入的洞察力，以及涉及癌症进展涉及的侵入性增长的一般机制。该应用的目的是了解一个Sema3d的体内功能，Sema3d，Sema3d，sema3d，sema3d，sema3d，sema3d，sema3d，sema3d，sema3d，sema craftratiish crigration crigration crigration sevenruct ze crigation ze severent ze severent ze severtrant ze。 SEMA3D在指导整个中线和地形图中的视网膜轴突中的作用将进行研究。此外，将研究SEMA3D在控制细胞运动中的作用，以测试SEMA3D诱导神经rest迁移的开始的假设，和/或保持迁移的神经rest流的分离。我们的策略是检查SEMA3D异位表达和SEMA3D功能丧失对这些系统发展的影响，以及生命生长锥的动态行为以及体内迁移神经rest细胞的动态行为。斑马鱼胚胎非常适合我们开发的方法的组合。使用转基因斑马鱼，在任何所需的发育阶段都可以在Select细胞中脱颖而出。此外，SEMA3D函数可以通过反义或主导负面方法来破坏。延时显微镜可以直接可视化生活生长锥或胚胎中迁移细胞的反应。因此，提出的实验可能会提供有关信号素如何调节视网膜轴突发育和体内环境中神经rest细胞迁移的新见解。