Role of caderhins in the developing zebrafish CV system

Bagatto, Brian

Abstract

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.