Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation

Abstract

Tubulogenesis is an essential component of organ development, yet the underlying cellular mechanisms are poorly understood. We analyze here the formation of the Drosophila melanogaster cardiac lumen that arises from the migration and subsequent coalescence of bilateral rows of cardioblasts. Our study of cell behavior using three-dimensional and time-lapse imaging and the distribution of cell polarity markers reveals a new mechanism of tubulogenesis in which repulsion of prepatterned luminal domains with basal membrane properties and cell shape remodeling constitute the main driving forces. Furthermore, we identify a genetic pathway in which roundabout, slit, held out wings, and dystroglycan control cardiac lumen formation by establishing nonadherent luminal membranes and regulating cell shape changes. From these data we propose a model for D. melanogaster cardiac lumen formation, which differs, both at a cellular and molecular level, from current models of epithelial tubulogenesis. We suggest that this new example of tube formation may be helpful in studying vertebrate heart tube formation and primary vasculogenesis.

Robo4

“…Recent findings published by two separate groups indicating Robo/Slit signaling involvement in Drosophila melanogaster heart tube lumen formation support this idea. 10,11 Drosophila melanogaster cardiac morphology comprises a simple linear tube, which is strikingly similar to vertebrate capillaries. It is therefore plausible that a repulsive signaling from Robo4/ Slit promotes tube formation by inhibiting E-cadherin-mediated cell adhesion at the apical surface (Fig.…”

Drosophila Model of Congenital Heart Diseases

“…Slit, an EGF-like ligand, and the Slit-receptor Roundabout (Robo) are both expressed by cardioblasts during morphogenesis and lumen formation, and ChIP data suggest that cardiac genes, such as tinman , directly regulate their expression. Mutants for slit or robo together with its paralogue robo2 have distinct defects during these processes (Qian et al, 2005b;MacMullin and Jacobs, 2006;SantiagoMartínez et al, 2006;Medioni et al, 2008;Santiago-Martínez et al, 2008): impaired cardioblasts cell-cell adhesion, which disrupts subsequent heart morphogenesis, and impairment of cell shape changes and lumen formation. In slit mutants, polar (or polarly distributed) markers, including the Drosophila MAGUK protein Discs-large, are incorrectly localized indicating a loss of overall cardioblast polarity (Qian et al, 2005b).…”

“…In slit mutants, polar (or polarly distributed) markers, including the Drosophila MAGUK protein Discs-large, are incorrectly localized indicating a loss of overall cardioblast polarity (Qian et al, 2005b). In addition, the cardioblasts fail to correctly change their cell shape in order to enclose a heart lumen (Medioni et al, 2008). This is accompanied by upregulation of the cell adhesion molecule Shotgun/E-Cadherin at the presumptive luminal domain, leading to increased adhesion at the luminal surfaces, which in www.intechopen.com turn is likely to prevent further lumen formation (Santiago-Martínez et al, 2008).…”

“…of the actin cytoskeleton, specifically in the heart. This allows the effects of specific mutations on actin dynamics to be monitored during heart formation (Medioni et al, 2008). Furthermore, a large number of fluorescently labeled genes such as actin GFP that can be overexpressed are readily available from different laboratories and stock centers.…”

Mechanisms of Lumen Development in Drosophila Tubular Organs

“…This polarization of Slit/Robo signaling is critical for its function in regulating lumen formation. In robo and slit mutants, E-cadherin mediated adhesion between the two opposing CBs is expanded preventing critical cell shape changes and blocking lumen formation (Medioni et al, 2008;Santiago-Martinez et al, 2008). In contrast, when Slit is ectopically expressed on all CB surfaces, a loss of cell adhesion was observed, resulting in the formation of multiple lumens (Santiago-Martinez et al, 2008).…”