Hippo Pathway Inhibits Wnt Signaling to Restrain Cardiomyocyte Proliferation and Heart Size
Year: 2011
Type: article
Abstract: 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.
Source: Science
Authors: Todd Heallen, Min Zhang, Jun Wang, Margarita Bonilla-Claudio, Ela Klysik, Randy L. Johnson, James F. Martin
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: G1498042361, Pitx2 Function in Cardiac Development, UT-H Comprehensive Research Training Program, Bmp-signaling in craniofacial development, Mechanisms of Veterbrate Dorsal-ventral Limb Patterning, G8134533947, Genetic Analysis of the Hippo Signaling Pathway in the Mouse Mammary Gland, G8876235112
OpenAlex ID: W2071765960