title: Endothelin-3 stimulates cell adhesion and cooperates with β1-integrins during enteric nervous system ontogenesis.
abstract: Endothelin-3 (EDN3) and β1-integrins are required for the colonization of the embryonic gut by enteric neural crest cells (ENCCs) to form the enteric nervous system (ENS). β1-integrin-null ENCCs exhibit migratory defects in a region of the gut enriched in EDN3 and in specific extracellular matrix (ECM) proteins. We investigated the putative role of EDN3 on ENCC adhesion properties and its functional interaction with β1-integrins during ENS development. We show that EDN3 stimulates ENCC adhesion to various ECM components in vitro. It induces rapid changes in ENCC shape and protrusion dynamics favouring sustained growth and stabilization of lamellipodia, a process coincident with the increase in the number of focal adhesions and activated β1-integrins. In vivo studies and ex-vivo live imaging revealed that double mutants for Itgb1 and Edn3 displayed a more severe enteric phenotype than either of the single mutants demonstrated by alteration of the ENS network due to severe migratory defects of mutant ENCCs taking place early during the ENS development. Altogether, our results highlight the interplay between the EDN3 and β1-integrin signalling pathways during ENS ontogenesis and the role of EDN3 in ENCC adhesion.
authors.affiliation: Institut Curie, CNRS, UMR144, Paris, 75005, France.|INSERM, U955, Team 6, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Gazquez
authors.affiliation: INSERM, U955, Team 6, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|INSERM, U955, Team 11, Créteil, 94000, France.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Institut Curie, CNRS, UMR144, Paris, 75005, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Broders-Bondon
authors.affiliation: Cell and Tissue Imaging Facility, PICT-IBiSA, Paris, 75005, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Paul-Gilloteaux
authors.affiliation: Institut Curie, CNRS, UMR144, Paris, 75005, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Heysch
authors.affiliation: INSERM, U955, Team 6, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|INSERM, U955, Team 11, Créteil, 94000, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Baral
authors.affiliation: INSERM, U955, Team 6, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.|INSERM, U955, Team 11, Créteil, 94000, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Bondurand
authors.affiliation: Institut Curie, CNRS, UMR144, Paris, 75005, France.|INSERM, U955, Team 6, Créteil, 94000, France.|Université Paris Est, Faculté de Médecine, Créteil, 94000, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dufour
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology; D003433:Crosses, Genetic; D003599:Cytoskeleton / Q000378:metabolism; D019334:Endothelin-3 / Q000378:metabolism*; D017615:Enteric Nervous System / Q000196:embryology*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D005838:Genotype; D019012:Integrin beta1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D008297:Male; D051379:Mice; D009154:Mutation; D009432:Neural Crest / Q000166:cytology; D010641:Phenotype; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019334:Endothelin-3; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1