Endothelin-3 stimulates cell adhesion and cooperates with β1-integrins during enteric nervous system ontogenesis.
Endothelin-3 stimulates cell adhesion and cooperates with β1-integrins during enteric nervous system ontogenesis.
复制标题
DOI：
10.1038/srep37877
复制
发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Dufour S
中科院分区：
文献类型：
--
作者：
Gazquez E;Watanabe Y;Broders-Bondon F;Paul-Gilloteaux P;Heysch J;Baral V;Bondurand N;Dufour S
内皮素-3(Endoelin-3，EDN-3)和β-1-整合素是肠道神经峰细胞(Encs)在胚胎肠道定植形成肠道神经系统(Ens)所必需的。β1整合素缺失的ENCC在肠道中富含EDN3和特定的细胞外基质蛋白的区域显示出迁移缺陷。我们研究了EDN3在ENCC黏附特性中的可能作用，以及它在ENS发育过程中与β-1整合素的功能相互作用。我们发现EDN3在体外刺激ENCC与各种ECM成分的黏附。它诱导ENCC形状和突起动力学的快速变化，有利于片状脂膜的持续生长和稳定，这一过程与局灶性粘连和激活的β1-整合素的数量增加相一致。体内研究和体外活体成像显示，由于突变的ENCCs在ENS发育早期发生了严重的迁移缺陷，Itgb1和Edn3的双突变株表现出比单一突变株更严重的肠道表型，这是由于ENS网络的改变。总之，我们的结果强调了EDN3和β1-整合素信号通路在ENS个体发育过程中的相互作用，以及EDN3在ENCC黏附中的作用。
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.
登录
查看更多内容
影响因子：
2.7
作者：
Broders-Bondon, Florence;Paul-Gilloteaux, Perrine;Dufour, Sylvie
通讯作者：
Dufour, Sylvie
影响因子：
10.5
作者：
FASSLER, R;MEYER, M
通讯作者：
MEYER, M
影响因子：
4.6
作者：
Chevalier NR;Gazguez E;Bidault L;Guilbert T;Vias C;Vian E;Watanabe Y;Muller L;Germain S;Bondurand N;Dufour S;Fleury V
通讯作者：
Fleury V
影响因子：
1.5
作者：
Druckenbrod, Noah R.;Powers, Patricia A.;Bartley, Christopher R.;Walker, Jeffery W.;Epstein, Miles L.
通讯作者：
Epstein, Miles L.
影响因子：
4.6
作者：
Faure, Sandrine;McKey, Jennifer;de Santa Barbara, Pascal
通讯作者：
de Santa Barbara, Pascal