title: Ephrin B1 maintains apical adhesion of neural progenitors.
abstract: Apical neural progenitors are polarized cells for which the apical membrane is the site of cell-cell and cell-extracellular matrix adhesion events that are essential for maintaining the integrity of the developing neuroepithelium. Apical adhesion is important for several aspects of the nervous system development, including morphogenesis and neurogenesis, yet the mechanisms underlying its regulation remain poorly understood. Here, we show that ephrin B1, a cell surface protein that engages in cell signaling upon binding cognate Eph receptors, controls normal morphogenesis of the developing cortex. Efnb1-deficient embryos exhibit morphological alterations of the neuroepithelium that correlate with neural tube closure defects. Using loss-of-function experiments by ex vivo electroporation, we demonstrate that ephrin B1 is required in apical progenitors (APs) to maintain their apical adhesion. Mechanistically, we show that ephrin B1 controls cell-ECM adhesion by promoting apical localization of integrin β1 and we identify ADP-ribosylation factor 6 (Arf6) as an important effector of ephrin B1 reverse signaling in apical adhesion of APs. Our results provide evidence for an important role for ephrin B1 in maintaining the structural integrity of the developing cortex and highlight the importance of tightly controlling apical cell-ECM adhesion for neuroepithelial development.
authors.affiliation: Centre de Biologie du Développement, CNRS, 118 Route de Narbonne, Bât 4R3, 31062 Toulouse cedex 9, France.
authors.forename: Dina N
authors.initials: DN
authors.lastname: Arvanitis
authors.forename: Annie
authors.initials: A
authors.lastname: Béhar
authors.forename: Petra
authors.initials: P
authors.lastname: Tryoen-Tóth
authors.forename: Jeff O
authors.initials: JO
authors.lastname: Bush
authors.forename: Thomas
authors.initials: T
authors.lastname: Jungas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vitale
authors.forename: Alice
authors.initials: A
authors.lastname: Davy
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D019521:Body Patterning; D001921:Brain / Q000196:embryology; D002448:Cell Adhesion; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018274:Electroporation; D036387:Ephrin-B1 / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D054259:Neural Tube / Q000196:embryology; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: D000089982:ADP-Ribosylation Factor 6; C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D020727:ADP-Ribosylation Factors; C000715727:Arf6 protein, mouse