Csk-deficient boundary cells are eliminated from normal Drosophila epithelia by exclusion, migration, and apoptosis
Csk-deficient boundary cells are eliminated from normal Drosophila epithelia by exclusion, migration, and apoptosis
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DOI：
10.1016/j.devcel.2005.11.007
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发表时间：
2006-01-01
影响因子：
11.8
通讯作者：
Cagan, RL
中科院分区：
文献类型：
--
作者：
Vidal, M;Larson, DE;Cagan, RL
正常上皮的构建和维持依赖于局部信号，这些信号引导细胞进入适当的壁龛并去除不需要的细胞。如果不能正确地执行这一过程，可能会导致异常发育或疾病，包括癌症和相关的转移。在这里，我们表明局部环境影响dcsk缺陷细胞的行为。dCsk的广泛缺失导致组织过度增生，细胞凋亡受阻，钙粘蛋白介导的粘附减少。离散斑块中dCsk的缺失导致不同的结果：上皮排斥、侵袭性迁移和凋亡性死亡。这些后一种表型需要邻居之间dCsk活性的显著差异；dE-cadherin、P120-catenin、Rhol、JNK和MMP2介导了这一信号。总之，我们的数据证明了细胞微环境如何在决定dCsk活性改变的结果中发挥核心作用，并揭示了p120 -连环蛋白在通过去除异常细胞来保护上皮完整性的机制中的作用。
The construction and maintenance of normal epithelia relies on local signals that guide cells into their proper niches and remove unwanted cells. Failure to execute this process properly may result in aberrant development or diseases, including cancer and associated metastasis. Here, we show that local environment influences the behavior of dCsk-deficient cells. Broad loss of dCsk led to enlarged and mispatterned tissues due to overproliferation, a block in apoptosis, and decreased cadherin-mediated adhesion. Loss of dCsk in discrete patches led to a different outcome: epithelial exclusion, invasive migration, and apoptotic death. These latter phenotypes required sharp differences in dCsk activity between neighbors; dE-cadherin, P120-catenin, Rhol, JNK, and MMP2 mediated this signal. Together, our data demonstrate how the cellular micro-environment plays a central role in determining the outcome of altered dCsk activity, and reveal a role for P120-catenin in a mechanism that protects epithelial integrity by removing abnormal cells.