Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway
Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway
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DOI：
10.1016/j.cub.2006.09.045
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发表时间：
2006-11-07
期刊：
影响因子：
9.2
通讯作者：
Harvey, Kieran F.
中科院分区：
文献类型：
--
作者：
Bennett, F. Christian;Harvey, Kieran F.
背景资料：长期以来，人们一直知道非典型脂肪钙粘蛋白控制果蝇的细胞增殖和器官大小，但脂肪控制这些过程的机制仍然难以捉摸。一个新出现的信号通路，控制器官大小在发展过程中是萨尔瓦多/疣/河马pathway.Results：在这里，我们表明，脂肪限制器官大小通过调节活动的萨尔瓦多/疣/河马途径。FT与该途径的正调控因子和负调控因子在遗传上相互作用，并且缺乏脂肪的组织密切表型模仿缺乏通常促进萨尔瓦多/疣/河马途径活性的基因的组织。缺乏脂肪的细胞比野生型细胞生长和增殖得更快，并且由于细胞周期蛋白E的表达升高而表现出延迟的细胞周期退出。脂肪突变细胞显示出对正常发育凋亡线索的部分不敏感性，并表达增加水平的抗凋亡DIAP 1蛋白。总的来说，这些缺陷导致脂肪突变动物的器官大小增加和生物体致死率增加。脂肪调节萨尔瓦多/疣/河马途径活动，促进丰富和本地化的扩展蛋白在顶端膜的上皮tissue.Conclusions：脂肪限制器官大小在果蝇发育过程中通过萨尔瓦多/疣/河马途径。这些研究有助于我们理解发育器官大小的控制，并对人类过度增殖性疾病（如癌症）有影响。
Background: The atypical Fat cadherin has long been known to control cell proliferation and organ size in Drosophila, but the mechanism by which Fat controls these processes has remained elusive. A newly emerging signaling pathway that controls organ size during development is the Salvador/Warts/Hippo pathway.Results: Here we demonstrate that Fat limits organ size by modulating activity of the Salvador/Warts/Hippo pathway. ft interacts genetically with positive and negative regulators of this pathway, and tissue lacking fat closely phenocopies tissue deficient for genes that normally promote Salvador/Warts/Hippo pathway activity. Cells lacking fat grow and proliferate more quickly than their wild-type counterparts and exhibit delayed cell-cycle exit as a result of elevated expression of Cyclin E. fat mutant cells display partial insensitivity to normal developmental apoptosis cues and express increased levels of the anti-apoptotic DIAP1 protein. Collectively, these defects lead to increased organ size and organism lethality in fat mutant animals. Fat modulates Salvador/Warts/Hippo pathway activity by promoting abundance and localization of Expanded protein at the apical membrane of epithelial tissues.Conclusions: Fat restricts organ size during Drosophila development via the Salvador/Warts/Hippo pathway. These studies aid our understanding of developmental organ size control and have implications for human hyperproliferative disorders, such as cancers.