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Rap1 促进生长组织中的上皮完整性和细胞活力。

Rap1 promotes epithelial integrity and cell viability in a growing tissue.

机构信息

Division of Biology, Kansas State University, Manhattan, KS, 66506, USA.

Division of Biology, Kansas State University, Manhattan, KS, 66506, USA.

出版信息

Dev Biol. 2023 Sep;501:1-19. doi: 10.1016/j.ydbio.2023.05.006. Epub 2023 Jun 2.

Abstract

Having intact epithelial tissues is critical for embryonic development and adult homeostasis. How epithelia respond to damaging insults or tissue growth while still maintaining intercellular connections and barrier integrity during development is poorly understood. The conserved small GTPase Rap1 is critical for establishing cell polarity and regulating cadherin-catenin cell junctions. Here, we identified a new role for Rap1 in maintaining epithelial integrity and tissue shape during Drosophila oogenesis. Loss of Rap1 activity disrupted the follicle cell epithelium and the shape of egg chambers during a period of major growth. Rap1 was required for proper E-Cadherin localization in the anterior epithelium and for epithelial cell survival. Both Myo-II and the adherens junction-cytoskeletal linker protein α-Catenin were required for normal egg chamber shape but did not strongly affect cell viability. Blocking the apoptotic cascade failed to rescue the cell shape defects caused by Rap1 inhibition. One consequence of increased cell death caused by Rap1 inhibition was the loss of polar cells and other follicle cells, which later in development led to fewer cells forming a migrating border cell cluster. Our results thus indicate dual roles for Rap1 in maintaining epithelia and cell survival in a growing tissue during development.

摘要

完整的上皮组织对于胚胎发育和成年期的内稳态至关重要。上皮组织在发育过程中如何在保持细胞间连接和屏障完整性的同时,对损伤性刺激或组织生长做出反应,目前还知之甚少。保守的小分子 GTPase Rap1 对于建立细胞极性和调节钙粘蛋白-连环蛋白细胞连接至关重要。在这里,我们确定了 Rap1 在维持果蝇卵子发生过程中上皮完整性和组织形状方面的新作用。Rap1 活性丧失破坏了滤泡细胞上皮和卵室的形状,而卵室在此期间经历了主要的生长。Rap1 对于上皮细胞中 E-Cadherin 的正确定位以及上皮细胞的存活是必需的。Myo-II 和黏着连接-细胞骨架连接蛋白α-Catenin 对于正常的卵室形状都是必需的,但对细胞活力的影响不大。阻断凋亡级联反应未能挽救由 Rap1 抑制引起的细胞形状缺陷。Rap1 抑制引起的细胞死亡增加的一个后果是极性细胞和其他滤泡细胞的丧失,这在以后的发育过程中导致形成迁移的边缘细胞簇的细胞更少。因此,我们的结果表明 Rap1 在发育过程中维持不断生长的组织中的上皮组织和细胞存活具有双重作用。

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