Cellular, Genetic and Descriptive Analysis of Drosophila Heart Development

Washington University School Of Medicine, Saint Louis MO

Investigators

Abstract

0077727 Skeath The elucidation of the molecular pathways that regulate heart development is critical to our understanding of heart formation. In humans, congenital heart defects are one of the most frequent birth defects and occur at an incidence of 1% in live births and 10% in stillborns. The genetic and molecular events that regulate heart development are just beginning to be explored in vertebrate and invertebrate model systems. Initial insights from this work demonstrate a remarkable conservation of structure, expression and function between Drosophila genes expressed in the developing heart and their vertebrate homologs. These studies as well as data from genome projects support the idea that the fundamental architecture of many biological processes are conserved between flies and humans. Thus, research that aims to understand the genetic, cellular and molecular mechanisms that control Drosophila heart development should yield basic insights into heart development in general. The focus of this grant is to dissect the developmental mechanisms that pattern and specify the identity of the different types of cells that make up the Drosophila heart. Present models of Drosophila heart development rely heavily on the analysis of the mechanisms that regulate the development of only a small minority (~10%) of heart cells. To obtain a more comprehensive picture of heart development, it is critical to clarify the genetic, cellular and molecular mechanisms that promote the development of all heart cells. The first specific aim of this grant proposes to create a gene expression, cell division and cell lineage map of all heart cells. The completion of this aim will establish a descriptive foundation of normal heart development at the single cell resolution from which we and others can initiate systematic studies on the genetic mechanisms that regulate heart development. The second specific aim proposes (i) to dissect the genetic regulatory mechanisms that pattern and specify the fate of all heart cells, and (ii) to perform a detailed phenotypic and molecular characterization of two genes that regulate the number of contractile cells that form in the heart. The integration of these approaches should paint an increasingly lucid picture of the genetic, cellular and molecular mechanisms that orchestrate Drosophila heart development.