Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus
Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus
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DOI：
10.1016/s0960-9822(03)00433-0
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发表时间：
2003-07-15
期刊：
影响因子：
9.2
通讯作者：
DeSimone, DW
中科院分区：
文献类型：
--
作者：
Marsden, M;DeSimone, DW
背景：会聚伸展运动是一种保守的组织重排，与多种形态发生事件有关。虽然许多涉及收敛延伸的细胞行为是已知的，但这一过程所需的分子相互作用仍然难以捉摸。结果：抗体阻断纤维连接蛋白(FN)的黏附或整合素β1功能的显性-负性抑制改变了钙粘附素介导的细胞黏附，促进了重组实验中的细胞分选行为，并抑制了原肠胚胎和外植体的内侧细胞嵌入和轴向伸展。胚胎外植体被用来证明正常的整合素信号是特定区域内的形态发生运动所必需的，而不是细胞命运指定所必需的。含有RGD的纤维连接蛋白的可溶性片段与整合素结合，促进分离的单细胞重新整合成完整的组织。所观察到的粘附性改变与钙粘素或整合素的表达水平无关。结论：整合素对钙粘附素粘附性的调节影响细胞在细胞外基质定义的边界内的嵌入行为。我们认为，这代表了在整个发育过程中促进局部细胞重排的基本机制。
Background: Convergence extension movements are conserved tissue rearrangements implicated in multiple morphogenetic events. While many of the cell behaviors involved in convergent extension are known, the molecular interactions required for this process remain elusive. However, past evidence suggests that regulation of cell adhesion molecule function is a key step in the progression of these behaviors.Results: Antibody blocking of fibronectin (FN) adhesion or dominant-negative inhibition of integrin beta1 function alters cadherin-mediated cell adhesion, promotes cell-sorting behaviors in reaggregation assays, and inhibits medial-lateral cell intercalation and axial extension in gastrulating embryos and explants. Embryo explants were used to demonstrate that normal integrin signaling is required for morphogenetic movements within defined regions but not for cell fate specification. The binding of soluble RGD-containing fragments of fibronectin to integrins promotes the reintegration of dissociated single cells into intact tissues. The changes in adhesion observed are independent of cadherin or integrin expression levels.Conclusions: We conclude that integrin modulation of cadherin adhesion influences cell intercalation behaviors within boundaries defined by extracellular matrix. We propose that this represents a fundamental mechanism promoting localized cell rearrangements throughout development.