Endothelin-3 stimulates cell adhesion and cooperates with ?1-integrins during enteric nervous system ontogenesis.

ABSTRACT: Endothelin-3 (EDN3) and ?1-integrins are required for the colonization of the embryonic gut by enteric neural crest cells (ENCCs) to form the enteric nervous system (ENS). ?1-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 ?1-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 ?1-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 ?1-integrin signalling pathways during ENS ontogenesis and the role of EDN3 in ENCC adhesion.

SUBMITTER: Gazquez E 

PROVIDER: S-EPMC5131347 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature