Date of Award

1-1-2011

Document Type

Campus Access Dissertation

Department

Biomedical Science

First Advisor

Jay D Potts

Abstract

Congenital heart defects (CHD) are the most common birth defect, occurring in nearly 1% of all live births. The majority of CHD are due to malformations of valve structure. During valve development, epithelial-mesenchymal transformation (EMT) is a key process to generate endocardial cushions at the atrioventricular (AV) canal and outflow tract (OFT). Subsequently, the AV endocardial cushions fuse and undergo remodeling to form the tricuspid and mitral valve leaflets as well as supporting structures, including chordae tendineae (CT). So far, a large number of genes and regulatory pathways involved in valvulogenesis have been identified using different animal models including zebrafish, chicken, and mouse. However, the cellular and molecular mechanisms of heart valve formation and maturation are still not well defined.

In the first part of the study, we investigated the role of zyxin, a focal adhesion protein, in EMT during chick AV valve morphogenesis. Expression and localization studies show that zyxin is distributed in the AV canal region at different stages of valve formation. Functional knockdown and overexpression studies reveal that zyxin plays a role in endocardial cell migration and cell differentiation during the EMT process. Thus, zyxin appears to play a role as a gatekeeper for cell migration and differentiation during EMT in AV valve formation. In the second part of the study, we examined the morphological and structural properties of chick chordate tendineae (CT) derived from the AV cushion. Scanning electron microscopy and laser confocal microscopy showed the distinctive morphological structure of type VI collagen between adult and embryonic chick CT. Taken together, our studies on EMT during AV valve morphogenesis and structural components of CT bring new insights into heart valve development.

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