Didier Stainier, Ph.D.

During metazoan development, groups of cells, often from different germ layers, come together to form the individual organs. As a paradigm to study organogenesis, we are focusing on the development of the heart. The embryonic heart is a simple structure which consists of two concentric epithelial tubes, the outer myocardial tube that forms the muscular component of the heart, and the inner endocardial tube that forms its endothelial lining.

We have elected to study heart development in the zebrafish, Danio rerio, because it offers unique advantages as a vertebrate genetic system and is also ideal for embryological studies. The zebrafish heart is accessible for continued observation and manipulation at all stages of development and offers single cell resolution of its components. Through several genome wide screen in zebrafish, we have identified a large number of mutations that affect heart formation and function.

We are currently using the tools of molecular biology, embryology and genetics to characterize some of these mutations and further our understanding of the cellular and molecular mechanisms underlying early cardiac morphogenesis. We are especially interested in studying early heart induction. Classical embryological studies have revealed potential roles for both the dorsal organizer and endodermal tissues in this process. We are thus making use of a number of mutations that affect either endodermal or myocardial differentiation to approach this problem. We are also interested in the differentiation of the endocardial cells and are analyzing a mutation called cloche where the heart is lacking the endocardial cells. Eight other mutations affect another aspect of cardiac morphogenesis as they block the fusion of the primitive myocardial tubes. This block results in the differentiation of two hearts, one on either side of the midline, a situation commonly known as cardia bifida. Several of these mutations affect endoderm development primarily and we have recently directed some of our attention towards this fascinating yet understudied germ layer.