Wnt信号通路
细胞生物学
河马信号通路
连环蛋白
SOX2
信号转导
生物
基因
转录因子
遗传学
作者
Todd R. Heallen,Min Zhang,Jun Wang,Margarita Bonilla-Claudio,Ela Klysik,Randy L. Johnson,James F. Martin
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2011-04-22
卷期号:332 (6028): 458-461
被引量:941
标识
DOI:10.1126/science.1199010
摘要
Genetic regulation of mammalian heart size is poorly understood. Hippo signaling represents an organ-size control pathway in Drosophila, where it also inhibits cell proliferation and promotes apoptosis in imaginal discs. To determine whether Hippo signaling controls mammalian heart size, we inactivated Hippo pathway components in the developing mouse heart. Hippo-deficient embryos had overgrown hearts with elevated cardiomyocyte proliferation. Gene expression profiling and chromatin immunoprecipitation revealed that Hippo signaling negatively regulates a subset of Wnt target genes. Genetic interaction studies indicated that β-catenin heterozygosity suppressed the Hippo cardiomyocyte overgrowth phenotype. Furthermore, the Hippo effector Yap interacts with β-catenin on Sox2 and Snai2 genes. These data uncover a nuclear interaction between Hippo and Wnt signaling that restricts cardiomyocyte proliferation and controls heart size.
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