Integrin α5β1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension
Integrin α5β1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension
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DOI：
10.1016/j.cub.2006.03.038
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发表时间：
2006-05-09
期刊：
影响因子：
9.2
通讯作者：
DeSimone, Douglas W.
中科院分区：
文献类型：
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作者：
Davidson, Lance A.;Marsden, Mungo;DeSimone, Douglas W.
背景：纤维连接蛋白的整合素识别是正常原肠胚形成所必需的，包括驱动蛙背轴趋同延伸和延伸的中外侧细胞嵌入行为；然而，所涉及的细胞和分子机制尚不清楚。结果：我们报道了在外植体制备过程中，纤维连接蛋白与反义morpholinos的消耗阻断了外植体的会聚伸展和中外侧突出行为。纤维连接蛋白的慢性耗损和与纤维连接蛋白结合的整合素α (5) β(1)的急性破坏都会增加极化细胞突起的频率和随机方向，这表明整合素-纤维连接蛋白的相互作用通常会抑制频繁的随机突起，而有利于较少的中外侧取向的突起。在没有整合素α (5) β(1)与纤维连接蛋白结合的情况下，趋同运动仍然发生，但导致趋同增厚而不是趋同延伸。结论：这些发现支持整合素信号在调节驱动轴向延伸的突起活动中的作用。我们假设纤维连接蛋白基质的平面空间排列，描绘了胚胎内的组织区室，对于促进插层细胞的生产性取向突起至关重要。
Background: Integrin recognition of fibronectin is required for normal gastrulation including the mediolateral cell intercalation behaviors that drive convergent extension and the elongation of the frog dorsal axis; however, the cellular and molecular mechanisms involved are unclear.Results: We report that depletion of fibronectin with antisense morpholinos blocks both convergent extension and mediolateral protrusive behaviors in explant preparations. Both chronic depletion of fibronectin and acute disruptions of integrin alpha(5)beta(1) binding to fibronectin increases the frequency and randomizes the orientation of polarized cellular protrusions, suggesting that integrin-fibronectin interactions normally repress frequent random protrusions in favor of fewer mediolaterally oriented ones. In the absence of integrin alpha(5)beta(1) binding to fibronectin, convergence movements still occur but result in convergent thickening instead of convergent extension.Conclusions: These findings support a role for integrin signaling in regulating the protrusive activity that drives axial extension. We hypothesize that the planar spatial arrangement of the fibrillar fibronectin matrix, which delineates tissue compartments within the embryo, is critical for promoting productive oriented protrusions in intercalating cells.