肝病晚期残留的肝脏细胞失去自我增殖能力，成熟的胆管细胞通过去分化为双功能前体细胞并进一步分化为成熟肝脏和胆管细胞参与再生修复，但针对调控胆管细胞转分化的重要因子和分子机制还不清楚。本项目利用斑马鱼为动物模型，以ENU 正向诱变筛选获得肝脏再生起始缺陷突变体SWU001 为前提；以定位克隆其致变基因reg1 为研究对象；以解决reg1 调控肝脏再生起始的功能机制研究为目标，拟开展以下研究内容：1）ENU诱变筛选获得突变体SWU001 及其肝脏再生缺陷分析；2）SWU001 突变体致变基因的定位克隆及其验证；3）Reg1 在肝脏再生中的表达模式和调控肝脏再生起始研究；4）Reg1 参与调控肝脏再生起始的分子机制研究。通过发育生物学、遗传学、分子生物学、细胞生物学等技术深入探讨并揭示reg1 在起始肝脏再生中的重要作用。本项目将进一步揭示调控肝脏再生起始的关键因子，对肝脏再生医学具有重要意义。

Following severe injury hepatocytes are increasingly senescent, the choliangiocytes will dedifferentiate into bipotential progenitor cells and then differentiate to mature hepatocytes and choliangiocytes to complete the regeneration. However, the mechanisms about the transdifferentiation of biliary duct to hepatocyte remains unclear. This subject uses zebrafish as animal model to positional clone the candidate gene of SWU001 and analyze the phenotype and mechanisms of reg1 in initiating the liver regeneration. The contents of the project contain four parts: 1) the phenotype analyzing of SWU001; 2) Positional clone the candidate gene of SWU001; 3) The expression pattern of reg1 in liver regeneration and it’s function the initiation of liver regeneration; 4) The molecular mechanism of Reg1 involved in regulating the initiation of liver regeneration. The aim of this study is to explore and reveal the important role of reg1 in the initiation of liver regeneration by the method of developmental biology, genetics, molecular biology and cellular biology. This project will further explore the key factors in regulating the initiation of liver regeneration, which is of great theoretical significance for the liver regenerative medicine.