Huang Yunxian, Gui Jinghua, Myllymäki Satu-Marja, Mikkola Marja L, Shimmi Osamu
Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.
iScience. 2023 Mar 22;26(4):106490. doi: 10.1016/j.isci.2023.106490. eCollection 2023 Apr 21.
Maintaining apicobasal polarity (ABP) is crucial for epithelial integrity and homeostasis during tissue development. Although intracellular mechanisms underlying ABP establishment have been well studied, it remains to be addressed how the ABP coordinates tissue growth and homeostasis. By studying Scribble, a key ABP determinant, we address molecular mechanisms underlying ABP-mediated growth control in the wing imaginal disc. Our data reveal that genetic and physical interactions between Scribble, Septate junction complex and α-Catenin appear to be key for sustaining ABP-mediated growth control. Cells with conditional knockdown instigate the loss of α-Catenin, ultimately leading to the formation of neoplasia accompanying with activation of Yorkie. In contrast, cells expressing wild type progressively restore ABP in hypomorphic mutant cells in a non-autonomous manner. Our findings provide unique insights into cellular communication among optimal and sub-optimal cells to regulate epithelial homeostasis and growth.
在组织发育过程中，维持顶端-基底端极性（ABP）对于上皮完整性和内环境稳定至关重要。尽管ABP建立的细胞内机制已得到充分研究，但ABP如何协调组织生长和内环境稳定仍有待解决。通过研究关键的ABP决定因素Scribble，我们探讨了翅成虫盘ABP介导的生长控制的分子机制。我们的数据表明，Scribble、分隔连接复合体和α-连环蛋白之间的遗传和物理相互作用似乎是维持ABP介导的生长控制的关键。条件性敲低的细胞会引发α-连环蛋白的丧失，最终导致伴随Yorkie激活的肿瘤形成。相反，表达野生型的细胞以非自主方式在亚形态突变细胞中逐渐恢复ABP。我们的研究结果为最佳和次优细胞之间的细胞通讯提供了独特见解，以调节上皮内环境稳定和生长。
