MGA是一个具有T-Box和bHLHzip双功能域的转录因子。作为PRC1.6的成员，MGA突变导致多种恶疾的发生。但到目前为止，关于MGA的功能和突变导致疾病发生的分子机制并不清楚。基因突变是引发先天性巨结肠（HSCR）一个非常重要的因素，某些基因突变或缺失是导致ENS发育异常的根本原因。我们在前期的工作中发现，Mga缺失导致斑马鱼有HSCR-Like的ENS发育缺陷，通过分析发现Mga与PRC1.6的成员Ring1b、Pcgf6蛋白互作，且ChIP-seq结果显示Mga与Ring1b在ENS发育关键基因启动子区域共定位。本项目拟以斑马鱼和小鼠胚胎干细胞为材料，从体外和在体分析Mga通过PRC1.6调控ENS发育的分子机制。本项目的实施和完成，将不仅首次揭示Mga可能是HSCR的一个候选基因，而且阐明Mga在ENS发育中的功能。

MGA is a dual specificity T-box/bHLHzip transcription factor. As a part of PRC1.6，MGA mutation results in a variety of malignant diseases. But so far, little is known about the function and molecular mechanisms of MGA in the development of disease. Gene mutation is a very important cause of HSCR. Some genes mutation or deletion are the root cause of abnormal development of ENS. In this project, we found that the loss of Mga in zebrafish leads to HSCR-like phenotype. Further analysis showed that Mga interacts with Ring1b and Pcgf6 in zebrafish. In addition, ChIP-seq results revealed colocalization of Mga and Ring1b in the promoter of key genes of ENS development. Therefore, we propose to use zebrafish and mouse embryonic stem cells to investigate the molecular mechanisms of Mga regulates the ENS development by PRC1.6 in vivo and in vitro. This study is not only the first time for us to reveal that Mga may be a candidate gene of HSCR, but also, will illustrate the function of Mga in the development of ENS.