Molecular mechanism of Lgl-Mahj mediated cell competition

在多细胞生物的发育过程中，单个细胞相互竞争以产生正确大小和形状的器官。 比它们的邻居更不适合的细胞被那些邻居诱导进行程序性细胞死亡。 邻近细胞感知和“比较”它们相对健康的机制仍然是个谜。在与细胞竞争相关的基因中，肿瘤抑制基因（nTSGs）特别令人感兴趣。这些基因的突变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附近时，它们通过细胞竞争而被淘汰。在这些背景下，如何在细胞死亡和增殖之间做出决定仍然不清楚。最近的研究发现，新发现的nTSG Lethal Giant Larvae（Lgl）的结合伴侣Mahjong（Mahj）也参与细胞竞争，Mahj的过量表达阻止了lgl突变细胞在嵌合体中的死亡，提示Mahj和Lgl属于调节细胞竞争的通路。该项目将确定mahj和lgl如何调节细胞竞争，以及这些途径如何决定细胞之间的竞争？的生与死。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，并将为细胞竞争的分子机制提供见解。该项目将涉及当地的学校、学生和教师。

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.