Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size

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Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
05:38

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells

Published on: February 12, 2021

Todd Heallen1, Min Zhang, Jun Wang

  • 1Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA.

Science (New York, N.Y.)
|April 23, 2011
PubMed

Insights

Hippo signaling restricts mammalian heart size by inhibiting cardiomyocyte proliferation. This pathway interacts with Wnt signaling, revealing a novel mechanism for controlling heart organ growth.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Mammalian heart size regulation is not well understood.
  • Hippo signaling is a known organ-size regulator in Drosophila.
  • Its role in mammalian heart development is unexplored.

Purpose of the Study:

  • To investigate the role of Hippo signaling in mammalian heart size control.
  • To determine if Hippo pathway components regulate cardiomyocyte proliferation.
  • To elucidate the interaction between Hippo and Wnt signaling in heart development.

Main Methods:

  • Inactivation of Hippo pathway components in developing mouse hearts.
  • Analysis of heart size and cardiomyocyte proliferation in mutant embryos.
  • Gene expression profiling and chromatin immunoprecipitation.
  • Genetic interaction studies with Wnt signaling components (β-catenin).

Main Results:

  • Hippo-deficient mouse embryos exhibited overgrown hearts with increased cardiomyocyte proliferation.
  • Hippo signaling was found to negatively regulate specific Wnt target genes.
  • β-catenin heterozygosity partially rescued the overgrowth phenotype.
  • The Hippo effector Yap was shown to interact with β-catenin on specific gene promoters (Sox2, Snai2).

Conclusions:

  • Hippo signaling acts as a crucial regulator of mammalian heart size.
  • A nuclear interaction between Hippo and Wnt signaling pathways restricts cardiomyocyte proliferation.
  • This cross-talk is essential for controlling heart organ growth.

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