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

Edgardo Santiago Martínez's picture
PDF versionPDF version
TitleRepulsion by Slit and Roundabout prevents Shotgun/E-cadherin-mediated cell adhesion during Drosophila heart tube lumen formation.
Publication TypeJournal Article
Year of Publication2008
AuthorsSantiago-Martínez, E, Soplop, NH, Patel, R, Kramer, SG
JournalJ Cell Biol
Volume182
Issue2
Pagination241-8
Date Published2008 Jul 28
ISSN1540-8140
KeywordsAnimals, Cadherins, Cell Adhesion, Cell Differentiation, Cell Membrane, Cell Polarity, Drosophila melanogaster, Drosophila Proteins, Endothelial Cells, Epithelial Cells, Focal Adhesions, Heart, Heart Defects, Congenital, Neovascularization, Physiologic, Nerve Tissue Proteins, Organogenesis, Receptors, Immunologic
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.

DOI10.1083/jcb.200804120
Alternate JournalJ. Cell Biol.
PubMed ID18663139
PubMed Central IDPMC2483515
Grant ListF31/GM75393 / GM / NIGMS NIH HHS / United States