Cadherin-11 mediates contact inhibition of locomotion during Xenopus neural crest cell migration.
Cadherin-11 mediates contact inhibition of locomotion during Xenopus neural crest cell migration.
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DOI：
10.1371/journal.pone.0085717
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kashef J
中科院分区：
文献类型：
--
作者：
Becker SF;Mayor R;Kashef J
集体细胞迁移是胚胎发育和癌症进展的基本特征。这些协调的定向细胞运动的分子机制仍然需要阐明。颅神经嵴（CNC）细胞在胚胎发育过程中的迁移是体内细胞集体迁移的一个很好的模型。这些高度能动和多能的细胞在整个胚胎中以确定的路线定向迁移。有趣的是，局部细胞间的相互作用似乎是方向性的关键力量。CNC细胞可以通过称为运动接触抑制（CIL）的排斥性细胞反应改变其迁移方向。细胞突起在同型细胞-细胞接触时塌陷，并且内部复极化导致朝向无细胞区域形成新的突起。Wnt/PCP信号传导被证明介导小RhoGTdR RhoA的激活和接触侧的细胞突起的抑制。然而，细胞如何识别接触的机制却知之甚少。在这里，我们证明了爪蟾钙粘蛋白-11（Xcad-11）介导的细胞-细胞粘附在CIL中是CNC细胞定向和集体迁移所必需的。Xcad-11粘附功能的降低由于CIL的丧失导致CNC的侵袭性更高。此外，移植分析显示，当Xcad-11粘附功能受损时，CNC在体内的迁移行为是非定向和不完整的。阻断Wnt/PCP信号传导导致了类似的结果，强调了Xcad-11在CIL机制和CNC定向迁移中的重要性。
Collective cell migration is an essential feature both in embryonic development and cancer progression. The molecular mechanisms of these coordinated directional cell movements still need to be elucidated. The migration of cranial neural crest (CNC) cells during embryogenesis is an excellent model for collective cell migration in vivo. These highly motile and multipotent cells migrate directionally on defined routes throughout the embryo. Interestingly, local cell-cell interactions seem to be the key force for directionality. CNC cells can change their migration direction by a repulsive cell response called contact inhibition of locomotion (CIL). Cell protrusions collapse upon homotypic cell-cell contact and internal repolarization leads to formation of new protrusions toward cell-free regions. Wnt/PCP signaling was shown to mediate activation of small RhoGTPase RhoA and inhibition of cell protrusions at the contact side. However, the mechanism how a cell recognizes the contact is poorly understood. Here, we demonstrate that Xenopus cadherin-11 (Xcad-11) mediated cell-cell adhesion is necessary in CIL for directional and collective migration of CNC cells. Reduction of Xcad-11 adhesive function resulted in higher invasiveness of CNC due to loss of CIL. Additionally, transplantation analyses revealed that CNC migratory behaviour in vivo is non-directional and incomplete when Xcad-11 adhesive function is impaired. Blocking Wnt/PCP signaling led to similar results underlining the importance of Xcad-11 in the mechanism of CIL and directional migration of CNC.
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影响因子：
4.6
作者：
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通讯作者：
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DOI：
10.1073/pnas.1019437108
发表时间：
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