Genome-Wide Approaches to Drosophila Heart Development

Abstract

The development of the dorsal vessel in Drosophila is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs into studies of cardiogenesis in vertebrates. Many of the major components that control Drosophila cardiogenesis were discovered based on candidate gene approaches and their functions were defined by employing the outstanding genetic tools and molecular techniques available in this system. More recently, approaches have been taken that aim to interrogate the entire genome in order to identify novel components and describe genomic features that are pertinent to the regulation of heart development. Apart from classical forward genetic screens, the availability of the thoroughly annotated Drosophila genome sequence made new genome-wide approaches possible, which include the generation of massive numbers of RNA interference (RNAi) reagents that were used in forward genetic screens, as well as studies of the transcriptomes and proteomes of the developing heart under normal and experimentally manipulated conditions. Moreover, genome-wide chromatin immunoprecipitation experiments have been performed with the aim to define the full set of genomic binding sites of the major cardiogenic transcription factors, their relevant target genes, and a more complete picture of the regulatory network that drives cardiogenesis. This review will give an overview on these genome-wide approaches to Drosophila heart development and on computational analyses of the obtained information that ultimately aim to provide a description of this process at the systems level.

Keywords: ChIP-chip; ChIP-seq; cardiogenesis; cardiogenic transcription factors; genetic screens; genomics; heart development; machine learning; transcriptomics.

Figure 1

Schematic drawings of dorsal vessels from late stage Drosophila embryo (A) and adult fly (B) (not to scale). The cell types discussed in the text are color-coded as indicated. The adult heart is remodeled from the larval dorsal vessel, which involves histolysis of cells from abdominal segments A6 and A7, transdifferentiation of the three anterior pairs of alary muscles into ventral longitudinal muscles (VLMs), differentiation of presumptive ostial cells from the larval aorta into functional ostia, formation of three valves, formation of the conical heart chamber, and a reduction in the number of pericardial cells.

Figure 2

Integration of genome-wide experimental approaches with computational and empirical studies in Drosophila cardiogenesis research.