Reference - Detail
|Author||Santiago-Martínez E, Soplop NH, Patel R, Kramer SG.|
|Title||Repulsion by Slit and Roundabout prevents Shotgun/E-cadherin-mediated cell adhesion during Drosophila heart tube lumen formation.|
|Journal||J. Cell Biol.|
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.
|MeSH||Animals Cadherins / genetics Cadherins / metabolism* Cell Adhesion / genetics Cell Differentiation / genetics Cell Membrane / genetics Cell Membrane / metabolism Cell Membrane / ultrastructure Cell Polarity / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / embryology* Drosophila melanogaster / metabolism Endothelial Cells / cytology Endothelial Cells / metabolism Epithelial Cells / cytology Epithelial Cells / metabolism Focal Adhesions / genetics Focal Adhesions / metabolism Focal Adhesions / ultrastructure Heart / embryology* Heart Defects, Congenital / genetics Heart Defects, Congenital / metabolism Heart Defects, Congenital / physiopathology Neovascularization, Physiologic / genetics Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Organogenesis / genetics Receptors, Immunologic / genetics Receptors, Immunologic / metabolism*|
|WOS Category||CELL BIOLOGY|