DSLMAP is a component of the developing heart tube and may interact with SlitRobo pathway in Drosophila

Title: DSLMAP is a component of the developing heart tube and may interact with SlitRobo pathway in Drosophila
Authors: Alhyari, Danya H
Date: 2010
Abstract: The Drosophila heart is composed of cardioblasts (CBs) and pericardial cells. Together, these cells form a linear heart tube that resembles the early vertebrate heart. Many genes involved in heart development are conserved from fruit flies to mammals. For example, the Drosophila homeobox gene Tinman and its vertebrate homologue Nkx2.5 are both critical for heart development. The secreted protein Slit and its receptor Roundabout (Robo) contribute to heart tube formation by guiding cardioblast alignment and adhesion. Slit null mutant showed severe alignment and migration defects, which include delays, gaps in the heart tube, and failure of lumen formation. Robo loss of function mutant also had severe defects which include, twisted heart tube, missing parts of the heart tube, and aggregation of the CBs. The Slit/Robo complex appears to serve conserved roles across species and in different systems by influencing cell guidance and migration. Previous studies have shown that sarcolemmal membrane associated protein (SLMAP) is expressed early during mammalian cardiac development and it may play role in cardiac function at the level of membrane biology and signal transduction. SLMAP and its homolog in Drosophila DSLMAP have similar structural features which include, a C-terminus transmembrane domain, a coiled-coil region, and a fork head associated domain at the N-terminus. DSLMAP and its mammalian homologue share 28.6% identity over 721 amino acid residues; a higher percentage identity was noted in the forkhead-associated domain (55.9%). Further more, DSLMAP were found to genetically interact with Slit/Robo pathway in the developing nervous system. Here, we show that DSLMAP is expressed in both the CBs and the pericardial cells at early stages of Drosophila heart development. Alterations in DSLMAP expression in the CBs, and the pericardial cells, using a UAS-DSLMAP-RNAi transgene causes a delay in migration of CBs and PCs, and misalignment of the cardiac cells. The up-regulation of DSLMAP in the CBs and the pericardial cells led to delay in migration of the cardiac cells, and to CBs aggregation. Down-regulation of DSLMAP has similar phenotypes to Robo down-regulation in both the CBs and the pericardial cells. In addition, over-expression of DSLMAP or Slit have the same phenotypes in the two cell types. Delayed migration defects are reduced by pericardial expression of UAS-DSLMAP RNAi in Robo down-regulated embryos. Myocardial expression of UAS-DSLMAP transgene suppresses the delayed migration defects seen in Slit over-expression. DSLMAP over-expression in the CBs significantly reduced the phenotypes seen in slit2 loss of function mutant. Over-expression of DSLMAP in the CBs of robo189 heterozygous background showed a significant reduction in the phenotypes observed in robo189 alone. DSLMAP down-regulation in the pericardial cells of slit2 heterozygous background, or robo189 heterozygous background led to a significant decrease in defective embryos and the heart tube was seem to be properly organised. The data suggests that DSLMAP is expressed early in cells that form the Drosophila heart, and its regulated levels are critical for normal heart tube formation. Data also suggests that DSLMAP may genetically interact with the Slit/Robo pathway to ensure proper heart tube formation.
URL: http://hdl.handle.net/10393/28749
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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