Molecular mechanism of Lgl-Mahj mediated cell competition

在多细胞生物体的发育过程中，单个细胞相互竞争，以产生大小和形状正确的器官。比它们的邻居更不适合的细胞被这些邻居诱导经历程序性细胞死亡。相邻细胞感觉和“比较”它们的相对适合度的机制仍然是个谜。在与细胞竞争相关的基因中，肿瘤抑制基因(NTSGs)尤其有趣。这些基因的突变会导致幼虫组织的过度增殖。在嵌合体的情况下，当突变细胞位于野生型细胞旁边时，它们会通过细胞竞争被淘汰。在这些背景下，如何在细胞死亡和增殖之间做出决定仍不清楚。最近的研究表明，新发现的ntsG致死巨型幼虫(LGL)的结合伙伴Mahjong(Mahj)也参与了细胞竞争，并且过表达Mahj可以阻止LGL突变细胞在嵌合体中经历细胞死亡，这表明Mahj和LGL属于调节细胞竞争的途径。这个项目将决定MAHJ和LGL如何调节细胞竞争，以及这些途径如何决定一个细胞的生死？S。这些研究将增加我们对正常细胞和转化细胞之间相互作用的理解，并将为深入了解细胞竞争的分子机制提供帮助。该项目将有来自当地的学校、学生和教师参与。

During the development of multicellular organisms, individual cells compete with one-another to produce organs of the correct size and shape. Cells less fit than their neighbors are induced by those neighbors to undergo programmed cell death. The mechanisms by which neighboring cells sense and "compare" their relative fitness are still mysterious. Among the genes related to cell competition, the neoplastic tumor-suppressor genes (nTSGs) are particularly interesting. Mutation of these genes results in over-proliferation of larval tissue. In a mosaic situation, the mutant cells are eliminated by cell competition when they are located next to wild-type cells. How the decision between cell death and proliferation is made in these backgrounds remains unclear. Recent study revealed that Mahjong (Mahj), a newly identified binding partner for nTSG Lethal Giant Larvae (Lgl), is also involved in cell competition, and over expression of Mahj prevents lgl mutant cells from undergoing cell death in mosaics, suggesting that Mahj and Lgl belong to the pathway regulating cellular competition. This project will determine how mahj and lgl regulate cell competition, and how these pathways decide between a cell?s life and death. These studies will increase our understanding of the interactions between normal and transformed cells and would provide insights into molecular mechanisms underlying cell competition. This project will involve schools, students and teachers from the local area.