N-cadherin and β1-integrins cooperate during the development of the enteric nervous system
N-cadherin and β1-integrins cooperate during the development of the enteric nervous system
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DOI：
10.1016/j.ydbio.2012.02.001
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发表时间：
2012-04-15
影响因子：
2.7
通讯作者：
Dufour, Sylvie
中科院分区：
文献类型：
--
作者：
Broders-Bondon, Florence;Paul-Gilloteaux, Perrine;Dufour, Sylvie
细胞黏附控制着胚胎的各种形态发生过程，包括肠道神经系统的发育。在小鼠的肠道神经脊细胞(ENCC)中去除β1整合素(beta 1-/-)的表达，导致肠道定植过程中ENCC的迁移减少和聚集特性增加，从而导致ENS结构的重大变化，从而导致先天性巨结肠的表型。在本研究中，我们研究了N-钙粘附素在ENS发育中的作用以及在这一过程中与β1整合素的相互作用。利用Ht-PA-Cre小鼠模型针对迁移性NCC中N-钙粘蛋白和β1整合素基因的破坏，产生这两种黏附受体的单条件和双条件突变。N-钙粘素和β1整合素双突变导致胚胎死亡，并在胚胎发育中存在严重缺陷N-钙粘素缺失(Ncad-/-)ENCC在E12.5表现出延迟在发育中的肠道的定植，尽管这比β1-/-突变的程度要小。Ncad-/-ENCC迁移的这种延迟在发育的后期阶段得到了恢复。双Ncad-/-；β1-/-突变体ENCC不能在肠道远端定植，并且近端后肠比N-钙粘素或β1-整合素单一突变体有更严重的无神经节细胞增多症。这是由于肠壁的运动速度和方向性发生了变化。在双突变体中未发现ENCC的异常聚集缺陷和神经节网络的紊乱。这表明N-钙粘素增强了β1-整合素突变的作用，并证实了这两种黏附受体在ENS个体发育过程中的协同作用。综上所述，我们的数据表明N-钙粘素对ENS的发育不是必需的，但它确实调节了ENCC的迁移模式，并与β1整合素协同作用，控制ENS的正常发育。(C)2012 Elsevier Inc.保留所有权利。
Cell adhesion controls various embryonic morphogenetic processes, including the development of the enteric nervous system (ENS). Ablation of beta 1-integrin (beta 1-/-) expression in enteric neural crest cells (ENCC) in mice leads to major alterations in the ENS structure caused by reduced migration and increased aggregation properties of ENCC during gut colonization, which gives rise to a Hirschsprung's disease-like phenotype. In the present study, we examined the role of N-cadherin in ENS development and the interplay with beta 1 integrins during this process. The Ht-PA-Cre mouse model was used to target gene disruption of N-cadherin and beta 1 integrin in migratory NCC and to produce single- and double-conditional mutants for these two types of adhesion receptors.Double mutation of N-cadherin and beta 1 integrin led to embryonic lethality with severe defects in ENS development N-cadherin-null (Ncad-/-) ENCC exhibited a delayed colonization in the developing gut at E12.5, although this was to a lesser extent than in beta 1-/- mutants. This delay of Ncad-/- ENCC migration was recovered at later stages of development. The double Ncad-/-; beta 1-/- mutant ENCC failed to colonize the distal part of the gut and there was more severe aganglionosis in the proximal hindgut than in the single mutants for N-cadherin or beta 1-integrin. This was due to an altered speed of locomotion and directionality in the gut wall. The abnormal aggregation defect of ENCC and the disorganized ganglia network in the beta 1-/- mutant was not observed in the double mutant. This indicates that N-cadherin enhances the effect of the beta 1-integrin mutation and demonstrates cooperation between these two adhesion receptors during ENS ontogenesis.In conclusion, our data reveal that N-cadherin is not essential for ENS development but it does modulate the modes of ENCC migration and acts in concert with beta 1 integrin to control the proper development of the ENS. (C) 2012 Elsevier Inc. All rights reserved.