Functional Analysis of the Role of Slit and its Receptors During D. melanogaster Heart Morphogenesis

Abstract

Proper formation of the heart is a critical developmental event which requires strict regulation of coordinated cardial cell adhesion, alignment, and migration. The simple, tube-like heart of the fruit fly, Drosophila melanogaster, has proven to be an attractive system in which to study the regulatory pathways which control cardiogenesis. This is mainly due to its strikingly similarity to the vertebrate heart during early embryogenesis. In addition, many genes identified in association with congenital heart disease in humans have homologues in Drosophila, suggesting that this model organism has great potential to contribute to cardiovascular research. The extracellular matrix protein encoded by slit is a ligand for the receptors Robo, and Robo2 (lea). Recently, a third receptor for Slit has been identified as the heparin sulfate proteoglycan Syndecan. The main objective of this thesis was to use time lapse confocal imaging in order to develop further understanding of the mechanisms which result in heart assembly defects in slit, robo, lea, and syndecan mutants. We also aimed to gain a better understanding of the role of Syndecan within the Slit-Robo pathway and elucidate its relative contribution to development of the mature heart. In mutants homozygous for slit, as well as mutants doubly heterozygous for robo and lea, cardial cell alignment, adhesion, and synchronized migration were disrupted. The heart phenotype of syndecan homozygous mutants was similar that of slit and robo, lea, however the migration speed of cells to the midline did not seem to be affected. Based on our findings, we hypothesize that Slit may have Syndecan-dependent and Syndecan-independent functions in the heart.