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J. Cell Biol. 182 (2): 241-248

Copyright © 2008 by the Rockefeller University Press.


Article

Repulsion by Slit and Roundabout prevents Shotgun/E-cadherin–mediated cell adhesion during Drosophila heart tube lumen formation

Edgardo Santiago-Martínez1,2, Nadine H. Soplop1,2, Rajesh Patel1, , and Sunita G. Kramer1,2

1 Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854
2 Joint Graduate Program in Cell and Developmental Biology, University of Medicine and Dentistry of New Jersey Graduate School of Biomedical Sciences and Rutgers, the State University of New Jersey, Piscataway, NJ 08854

Correspondence to Sunita G. Kramer: kramersg{at}umdnj.edu

Abstract: During Drosophila melanogaster heart development, a lumen forms between apical surfaces of contralateral cardioblasts (CBs). We show that Slit and its receptor Roundabout (Robo) are required at CB apical domains for lumen formation. Mislocalization of Slit outside the apical domain causes ectopic lumen formation and the mislocalization of cell junction proteins, E-cadherin (E-Cad) and Enabled, without disrupting overall CB cell polarity. Ectopic lumen formation is suppressed in robo mutants, which indicates robo's requirement for this process. Genetic evidence suggests that Robo and Shotgun (Shg)/E-Cad function together in modulating CB adhesion. robo and shg/E-Cad transheterozygotes have lumen defects. In robo loss-of-function or shg/E-Cad gain-of-function embryos, lumen formation is blocked because of inappropriate CB adhesion and an accumulation of E-Cad at the apical membrane. In contrast, shg/E-Cad loss-of-function or robo gain-of-function blocks lumen formation due to a loss of CB adhesion. Our data show that Slit and Robo pathways function in lumen formation as a repulsive signal to antagonize E-Cad–mediated cell adhesion.

Abbreviations used in this paper: Baz, Bazooka; CB, cardioblast; Dlg, Discs-large; E-Cad, E-cadherin; Ena, Enabled; GOF, gain of function; LOF, loss of function; PC, pericardial cell; Robo, roundabout; Shg, shotgun; XS, cross section.

© 2008 Santiago-Martínez et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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