Hippo signaling impedes adult heart regeneration

Todd Heallen; Yuka Morikawa; John Leach; Ge Tao; James T. Willerson; Randy L. Johnson; James F. Martin

doi:10.1242/dev.102798

journal article Dec 01, 2013

Hippo signaling impedes adult heart regeneration

Todd Heallen Yuka Morikawa

John Leach Ge Tao James T. Willerson Randy L. Johnson James F. Martin

Development Vol. 140 No. 23 pp. 4683-4690 · The Company of Biologists

View at Publisher Save 10.1242/dev.102798

Abstract

Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control pathway, is a kinase cascade that inhibits developing cardiomyocyte proliferation but it has not been studied postnatally or in fully mature adult cardiomyocytes. Here, we investigated Hippo signaling in adult cardiomyocyte renewal and regeneration. We found that unstressed Hippo-deficient adult mouse cardiomyocytes re-enter the cell cycle and undergo cytokinesis. Moreover, Hippo deficiency enhances cardiomyocyte regeneration with functional recovery after adult myocardial infarction as well as after postnatal day eight (P8) cardiac apex resection and P8 myocardial infarction. In damaged hearts, Hippo mutant cardiomyocytes also have elevated proliferation. Our findings reveal that Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration. Targeting the Hippo pathway in human disease might be beneficial for the treatment of heart disease.

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Metrics

428

Citations

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References

Details

Published: Dec 01, 2013
Vol/Issue: 140(23)
Pages: 4683-4690

Authors

T

Todd Heallen

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Y

Yuka Morikawa

Texas Heart Institute, Houston, TX 77030, USA.

J

John Leach

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

G

Ge Tao

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

J

James T. Willerson

Texas Heart Institute, Houston, TX 77030, USA.

R

Randy L. Johnson

Program in Developmental Biology, Baylor College of Medicine, One Baylor, Plaza, Houston, TX 77030, USA.; Department of Biochemistry and Molecular Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.

J

James F. Martin

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.; Texas Heart Institute, Houston, TX 77030, USA.; Program in Developmental Biology, Baylor College of Medicine, One Baylor, Plaza, Houston, TX 77030, USA.

Cite This Article

Todd Heallen, Yuka Morikawa, John Leach, et al. (2013). Hippo signaling impedes adult heart regeneration. Development, 140(23), 4683-4690. https://doi.org/10.1242/dev.102798

Hippo signaling impedes adult heart regeneration

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