同源异型框蛋白Msx1在肢体正常发育中起着重要的作用，其异常表达造成肢体出生缺陷。解析Msx1在肢体发育中的靶标基因特异性将有助于我们了解因其异常造成肢体缺陷的分子机制。申请人研究表明 Msx1在肢体发育过程中招募PRC2复合物到细胞核核周并重新分配H3K27me3到细胞核核周。因此申请人对Msx1在体内如何获得靶标基因特异性提出如下假设：Msx1选择性的识别、调控靶标基因，以及胚胎发育中不同时间和空间上对靶标基因的差异调控。本项目拟进行以下几方面研究：Msx1靶标基因体内识别的分子基础；Msx1体内调控靶标基因的分子机制；以及在肢体发育和再生中Msx1靶标基因的差异调控。该研究将阐明Msx1在体内获得靶标基因特异性的分子机制。研究结果将帮助人们了解Msx1在肢体发育和再生中的精细分子作用，并为了解肢体出生缺陷的分子机制提供坚实的理论基础，同时也为研究其他转录调控因子提供了有益的研究模式。

The homeoprotein Msx1 involved in normal limb development and that also contribute to limb defects if altered during development. Deciphering Msx1 target genespecificity will help us to understand the molecular events that contribute to limb defects. Msx1 recruit PRC2 complex to the periphery and redistributes the Polycomb H3K27me3 mark to the periphery in the developing limb (Dev Cell 21: 575-588, 2011). My studies have led to the hypothesis that target gene specificity in vivo represents the dynamic interplay of: selective recognition and regulation of target genes; anddifferential regulation in appropriate spatial and temporal embryonic contexts. These aspects of target gene specificity will be investigated the following: investigate molecular bases of target gene recognition by Msx1 in vivo. Investigate the mechanisms by which Msx1 regulates target gene expression in vivo. Investigate the differential regulation of Msx1 target genes in limb regeneration. This study will provide the insight molecular mechanisms of how Msx1 achieve target gene specificity in vivo. The findings will help us to understand the molecular roles of Msx1 during limb development as well as regeneration, andto understand the molecular events that contribute to limb defects, but also provide a useful research modelfor the study of other transcription factors.