Discovering Small Molecules that Promote Heart Development and Regeneration

• 作 者: PengXiangwen[1]TaoP.Zhong[1]NiTerri[2]YuGuangjiu[1]ShuHaibo[1]EricJ.Rellinger[2]XieShuying[1]YangHao[1]LiuPeiyun[1]AntonisHatzopoulos[2]
• 机 构: State Key Laboratory of Genetic Engineering,Department of Genetics,Fudan University School of Life S
• 出 处: 第三届全国斑马鱼研究大会
• 发表日期: 2013年期

　　We have developed a robust in vivo small-molecule screen that modulates heart size and cardiomyocyte generation in zebrafish.Three structurally related compounds(Cardionogen-1 to Cardionogen-3)identified from our screen enlarge the size of the developing heart via myocardial hyperplasia.Increased cardiomyocyte number in Cardionogen-treated embryos is due to expansion of cardiac progenitor cells.In zebrafish embryos and murine embryonic stem(ES)cells,Cardionogen treatment promotes cardiogenesis during and after gastrulation,whereas it inhibits heart formation before gastrulation.Cardionogen-induced effects can be antagonized by increasing Wnt/β-catenin signaling activity.We demonstrate that Cardionogen inhibits Wnt/β-catenin-dependent transcription in murine ES cells and zebrafish embryos.Cardionogen can rescue Wnt8-induced cardiomyocyte deficiency and heart specific phenotypes during development.Currently,we are in the process of testing whether Cardionogen compound family stimulates cardiomyocyte and heart regeneration.These findings demonstrate that in vivo small-molecule screens can reveal compounds with cardiomyogenic effects and identify underlying target pathways.