Role of integrins in mouse eyelid development: studies in normal embryos and embryos in which there is a failure of eyelid fusion
Role of integrins in mouse eyelid development: studies in normal embryos and embryos in which there is a failure of eyelid fusion
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DOI：
10.1016/s0925-4773(98)00145-2
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发表时间：
1998-11-01
影响因子：
2.6
通讯作者：
Watt, FM
中科院分区：
文献类型：
--
作者：
Carroll, JM;Luetteke, NC;Watt, FM
眼皮融合通常发生在小鼠胚胎发育的E15.5和E16.5之间，是一群周皮来源的上皮细胞在角膜表面迁移的结果。细胞迁移依赖于整合素家族的细胞外基质受体，并受生长因子的调节。因此，我们感兴趣的是，有报道称，在转化生长因子α(TCF-α)基因纯合缺失的小鼠和在总蛋白启动子控制下的转基因α(5)β(1)整合素在分化角质形成细胞中错误表达的小鼠中，眼皮融合失败。我们检测了α(2)β(1)、α(3)β(1)、α(5)β(1)和α(6)β(4)整合素在野生型胚胎眼睑融合过程中的表达，发现在迁移的眼睑尖细胞中，α(5)β(1)整合素及其配体纤维连接蛋白选择性上调。在转化生长因子α缺失的胚胎中，眼皮融合的失败与顶端细胞中α(5)β(1)、整合素和纤维连接蛋白上调的失败有关。以β-半乳糖苷酶为报告基因，在转基因小鼠的眼睑尖细胞中观察到了总蛋白启动子的特异性活性。在invα(5)beta(1)小鼠中，转基因人整合素不仅在尖端细胞中过表达，而且在整个眼皮表皮中都过表达。相比之下，内源性的，小鼠。α(5)β(1)整合素仅在TIP细胞中弱表达。我们推测，α(5)β(1)整合素和纤维连接蛋白在眼睑融合细胞中的选择性和协调表达是眼睑融合所必需的，可能受包括转化生长因子-α在内的生长因子的控制。(C)1998爱思唯尔爱尔兰科学有限公司。保留所有权利。
Eyelid fusion normally occurs between E15.5 and E16.5 of mouse embryonic development and results from the migration of a population of periderm-derived epithelial cells over the corneal surface. Cell migration is known to depend on extracellular matrix receptors of the integrin family and to be regulated by growth factors. We were therefore interested thar a failure of eyelid fusion has been reported in mice that are homozygous null for the transforming growth factor alpha (TCF-alpha) gene and in mice (inv alpha(5)beta(1)) in which a transgenic alpha(5)beta(1) integrin under the control of the involucrin promoter is misexpressed in differentiating keratinocytes. We examined expression of the alpha(2)beta(1), alpha(3)beta(1), alpha(5)beta(1) and alpha(6)beta(4) integrins during eyelid fusion in wild-type embryos and found selective upregulation of the alpha(5)beta(1) integrin and its ligand, fibronectin, in the migrating eyelid tip cells. In TGF-alpha null embryos, the failure of eyelid fusion was correlated with a failure to upregulate the alpha(5)beta(1), integrin and fibronectin in the tip cells. Using beta-galactosidase as a reporter gene in transgenic mice, we observed specific activity of the involucrin promoter in the eyelid tip cells. In inv alpha(5)beta(1) mice the transgenic human integrin was overexpressed not only in the tip cells but throughout the eyelid epidermis. In contrast, the endogenous, murine. alpha(5)beta(1) integrin was only weakly expressed in the tip cells. We speculate that selective and coordinated expression of the alpha(5)beta(1) integrin and fibronectin in eyelid tip cells is required for eyelid fusion and may be under the control of growth factors that include TGF-alpha. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.