Cadherins function in the developing zebrafish RGCs

钙粘蛋白在斑马鱼 RGC 发育中发挥作用

• 批准号: 6695940
• 负责人: QIN LIU
• 金额: $ 14.7万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695940
• 关键词: axon; cadherins; cell adhesion molecules; dendrites; developmental neurobiology; immunocytochemistry; neurogenesis; neuronal guidance; neutralizing antibody; optic nerve; protein binding; protein structure function; retinal ganglion; synaptogenesis; visual pathways; zebrafish

DESCRIPTION (provided by applicant): The long-term objective of this research is to determine how coordinated and differential cell adhesion regulates the development of the zebrafish visual system, with special emphasis on the role of cadherin cell adhesion molecules in the development of retinal ganglion cells. Cadherins are important cell adhesion molecules that have been implicated in the development of a variety of tissues and organs including the nervous system. Both in vitro and in vivo studies using a variety of vertebrate species have shown that cadherins are involved in retinal axon fasciculation, axonal outgrowth and pathfinding. However, most of the studies to date have focused on cadherin-2 (N-cadherin), and there is relatively little information on the roles, and in particular the in vivo functions, of other cadherins, in these processes. Moreover, little is known about relative roles of different cadherins in the development of retinal ganglion cells. We have studied expression patterns of both cadherin-2 and cadherin-4 (R-cadherin) in the visual system of developing zebrafish. I propose to study cadherin-2 and cadherin-4 function in zebrafish retinal ganglion cell development. This proposal has two specific aims: A) determine function of cadherin-4 in the development of zebrafish retinal ganglion cells, and B) determine function of cadherin-2 in the development of zebrafish retinal ganglion cells, and compare its function in retinal ganglion cell development with cadherin-4. A variety of techniques (e.g. application of cadherin antibodies, cadherin dominant-negative constructs, examination of cadherin-2 mutant) will be used in the project. The proposed studies, designed to uncover mechanisms underlying retinal ganglion cell development, may provide insights into therapies for injured or congenitally defective human retinal and optic nerve tissues.

描述（由申请人提供）：本研究的长期目标是确定协调和差异的细胞粘附如何调节斑马鱼视觉系统的发育，特别强调钙粘蛋白细胞粘附分子在视网膜神经节发育中的作用细胞。钙粘蛋白是重要的细胞粘附分子，与包括神经系统在内的多种组织和器官的发育有关。使用多种脊椎动物进行的体外和体内研究表明，钙粘蛋白参与视网膜轴突束颤、轴突生长和寻路。然而，迄今为止的大多数研究都集中在钙粘蛋白-2（N-钙粘蛋白）上，而关于其他钙粘蛋白在这些过程中的作用，特别是体内功能的信息相对较少。此外，人们对不同钙粘蛋白在视网膜神经节细胞发育中的相对作用知之甚少。我们研究了 cadherin-2 和 cadherin-4 (R-cadherin) 在发育中的斑马鱼视觉系统中的表达模式。我建议研究 cadherin-2 和 cadherin-4 在斑马鱼视网膜神经节细胞发育中的功能。该提案有两个具体目的：A）确定cadherin-4在斑马鱼视网膜神经节细胞发育中的功能，B）确定cadherin-2在斑马鱼视网膜神经节细胞发育中的功能，并比较其在视网膜神经节细胞中的功能与cadherin-4一起开发。该项目将使用多种技术（例如钙粘蛋白抗体的应用、钙粘蛋白显性失活构建体、钙粘蛋白-2突变体的检查）。拟议的研究旨在揭示视网膜神经节细胞发育的机制，可能为受伤或先天缺陷的人类视网膜和视神经组织的治疗提供见解。