POWRE: Echocardiographic Analysis of Developing Mouse and Chicken Hearts

Case Western Reserve University, Cleveland OH

Investigators

Abstract

0074882 Watanabe The outflow tract (OFT) is a critical portion of the developing and mature heart that connects the ventricles to the great vessels. This structure first appears as a simple tubular structure and undergoes septation, shortening, and rotation within days. Dr. Watanabe has shown that the OFT myocardium of the chicken embryo exhibits a high level of programmed cell death at a time when this tubular structure is shortening. She has have recently found that inducing higher or lower than normal levels of apoptosis specifically in that tissue results in cardiac defects. These results suggest that a regulated level of apoptosis of the OFT cardiomyocytes is critical to the proper alignment of the vessels to the ventricular chambers. The objectives are: (1) Determine whether programmed cell death occurs in the mouse outflow tract myocardium during critical stages in cardiogenesis. If positive, it would support apoptosis as an evolutionarily conserved cellular mechanism for sculpting the OFT myocardium. Standard histological techniques will be used as well as an assay for apoptosis (TUNEL) detecting DNA fragments. (2) Describe the function of the mouse heart using echocardiographic parameters (e.g. peak outflow velocity) as it undergoes a transition from a single to double circuited heart and compare to the OFT morphology. This would serve as the baseline for analyses of mutant mice to be carried out in the future. The applicant has been using the chicken embryo to investigate cardiogenesis, more specifically, the mechanisms by which the cardiac conduction system and the cardiac outflow tract develop. The utilization of the mouse model would complement and expand the current investigations as would introduction of a new functional assay, echocardiography. The funding provided by this POWRE grant would allow the applicant to learn (1) the anatomy of mouse heart at the critical stages of cardiogenesis and (2) application of echocardiography to the study of small animals.