Publication Date:
2011-04-23
Description:
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 beta-catenin heterozygosity suppressed the Hippo cardiomyocyte overgrowth phenotype. Furthermore, the Hippo effector Yap interacts with beta-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133743/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133743/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heallen, Todd -- Zhang, Min -- Wang, Jun -- Bonilla-Claudio, Margarita -- Klysik, Ela -- Johnson, Randy L -- Martin, James F -- R01 DE012324/DE/NIDCR NIH HHS/ -- R01 DE012324-12/DE/NIDCR NIH HHS/ -- R01 HD052785/HD/NICHD NIH HHS/ -- R01 HD052785-05/HD/NICHD NIH HHS/ -- R01 HD060579/HD/NICHD NIH HHS/ -- R01 HD060579-02/HD/NICHD NIH HHS/ -- R01 HL093484/HL/NHLBI NIH HHS/ -- R01 HL093484-01A1/HL/NHLBI NIH HHS/ -- R01HD052785/HD/NICHD NIH HHS/ -- R01HD060579/HD/NICHD NIH HHS/ -- T32 DE15355-04/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):458-61. doi: 10.1126/science.1199010.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21512031" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/metabolism
;
Animals
;
Cardiomegaly/metabolism
;
Cell Cycle Proteins/genetics/metabolism
;
Cell Nucleus/metabolism
;
Cell Proliferation
;
Chromatin Immunoprecipitation
;
Gene Expression Profiling
;
Gene Expression Regulation, Developmental
;
Heart/*anatomy & histology/embryology
;
Mice
;
Mice, Transgenic
;
Myocardium/cytology
;
Myocytes, Cardiac/*cytology/*metabolism
;
Organ Size
;
Phosphoproteins/metabolism
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/genetics/*metabolism
;
SOXB1 Transcription Factors/genetics/metabolism
;
*Signal Transduction
;
Transcription Factors/genetics/metabolism
;
Wnt Proteins/*metabolism
;
beta Catenin/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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