Role of caderhins in the developing zebrafish CV system

钙蛋白在斑马鱼CV系统发育中的作用

基本信息

批准号：
6952904
负责人：
BRIAN P BAGATTO
金额：
$ 22.05万
依托单位：
UNIVERSITY OF AKRON
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-15 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6952904
关键词：
antisense nucleic acid cadherins cardiogenesis developmental genetics digital imaging gene expression heart function immunocytochemistry morphology nonmammalian vertebrate embryology oligonucleotides protein structure function regeneration zebrafish

项目摘要

DESCRIPTION (provided by applicant): The long-term objectives of this project are to determine the roles of cadherin molecules in the development of the zebrafish cardiovascular system, with special emphasis on the heart. Cadherins are important cell adhesion molecules that have been implicated in the development of a variety of tissues and organs including the cardiac system. Cadherin-2 expression and function will be studied in the heart of the developing zebrafish and in the regenerating heart of adult zebrafish, with the following three specific aims: 1) determine the expression patter of cadherin-2 in the developing zebrafish heart, 2) determine the role of cadherin-2 in the development and function of the developing zebrafish heart, and 3) determine expression pattern of cadherin-2 in the normal and regenerating adult zebrafish heart. Expression patterns during development and regeneration will be determined using immunocytochemistry. In vivo embryonic cardiac function will be assessed using standardized digital imaging techniques and adult cardiac function during regeneration will be assessed using a micro-pressure system. Cadherin-2 production will be altered during development using morpholino antisense oligonucleotide technology and by expressing a cadherin-2 dominant negative construct at critical times during heart development. The use of glass onion (cadherin-2) mutant zebrafish will also be a major aspect of this study. The merits of this project revolve around two major aspects. First, the project routes a line of cadherin research into an extremely important and cutting edge area of cardiac development and regeneration. This will provide beneficial results and insight not only to the developmental research community, but also to the vertebrate (namely human) cardiac research community. Second, this project goes one step beyond a molecular expression analysis and truly ties a molecule with in vivo function and attempts to derive mechanistic interactions. These strengths together will produce a truly original and significant study.

描述（由申请人提供）：该项目的长期目标是确定钙粘蛋白分子在斑马鱼心血管系统（特别是心脏）发育中的作用。钙粘蛋白是重要的细胞粘附分子，与包括心脏系统在内的多种组织和器官的发育有关。将在发育中的斑马鱼心脏和成年斑马鱼的再生心脏中研究 Cadherin-2 的表达和功能，具有以下三个具体目标：1）确定 cadherin-2 在发育中的斑马鱼心脏中的表达模式，2）确定 cadherin-2 在斑马鱼心脏发育和功能中的作用，以及 3) 确定 cadherin-2 在正常和再生成体中的表达模式斑马鱼的心脏。将使用免疫细胞化学来确定发育和再生期间的表达模式。将使用标准化数字成像技术评估体内胚胎心脏功能，并使用微压力系统评估再生过程中的成人心脏功能。使用吗啉代反义寡核苷酸技术并通过在心脏发育过程中的关键时刻表达钙粘蛋白-2显性失活构建体，在发育过程中将改变钙粘蛋白-2的产生。玻璃洋葱 (cadherin-2) 突变斑马鱼的使用也将是这项研究的一个主要方面。该项目的优点主要集中在两个方面。首先，该项目将一系列钙粘蛋白研究引入心脏发育和再生的极其重要和前沿的领域。这不仅将为发育研究界，而且为脊椎动物（即人类）心脏研究界提供有益的结果和见解。其次，该项目超越了分子表达分析，真正将分子与体内功能联系起来，并试图推导出机械相互作用。这些优势结合在一起将产生真正原创且有意义的研究。