PMID- 21512031
OWN - NLM
STAT- MEDLINE
DCOM- 20110505
LR  - 20240104
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 332
IP  - 6028
DP  - 2011 Apr 22
TI  - Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and 
      heart size.
PG  - 458-61
LID - 10.1126/science.1199010 [doi]
AB  - 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.
FAU - Heallen, Todd
AU  - Heallen T
AD  - Institute of Biosciences and Technology, Texas A&M System Health Science Center, 
      2121 West Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Zhang, Min
AU  - Zhang M
FAU - Wang, Jun
AU  - Wang J
FAU - Bonilla-Claudio, Margarita
AU  - Bonilla-Claudio M
FAU - Klysik, Ela
AU  - Klysik E
FAU - Johnson, Randy L
AU  - Johnson RL
FAU - Martin, James F
AU  - Martin JF
LA  - eng
SI  - GEO/GSE27259
GR  - R01HD052785/HD/NICHD NIH HHS/United States
GR  - R01 HL093484-01A1/HL/NHLBI NIH HHS/United States
GR  - R01 HD052785/HD/NICHD NIH HHS/United States
GR  - R01 HD060579/HD/NICHD NIH HHS/United States
GR  - T32 DE015355/DE/NIDCR NIH HHS/United States
GR  - R01 DE012324-12/DE/NIDCR NIH HHS/United States
GR  - R01 HL093484/HL/NHLBI NIH HHS/United States
GR  - R01 HD052785-05/HD/NICHD NIH HHS/United States
GR  - R01 HD060579-02/HD/NICHD NIH HHS/United States
GR  - 10POST4140029/AHA/American Heart Association-American Stroke Association/United 
      States
GR  - T32 DE15355-04/DE/NIDCR NIH HHS/United States
GR  - R01HD060579/HD/NICHD NIH HHS/United States
GR  - 09PRE2150024/AHA/American Heart Association-American Stroke Association/United 
      States
GR  - R01 DE012324/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 0 (Sav1 protein, mouse)
RN  - 0 (Snai2 protein, mouse)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Sox2 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Wnt Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, mouse)
RN  - 0 (beta Catenin)
RN  - 0 (sna protein, Drosophila)
RN  - EC 2.7.1.- (Stk4 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Serine-Threonine Kinase 3)
RN  - EC 2.7.11.1 (Stk3 protein, mouse)
SB  - IM
CIN - Science. 2011 Apr 22;332(6028):426-7. PMID: 21512022
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Cardiomegaly/metabolism
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cell Nucleus/metabolism
MH  - Cell Proliferation
MH  - Chromatin Immunoprecipitation
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental
MH  - Heart/*anatomy & histology/embryology
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocardium/cytology
MH  - Myocytes, Cardiac/*cytology/*metabolism
MH  - Organ Size
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - SOXB1 Transcription Factors/genetics/metabolism
MH  - Serine-Threonine Kinase 3
MH  - *Signal Transduction
MH  - Snail Family Transcription Factors
MH  - Transcription Factors/genetics/metabolism
MH  - Wnt Proteins/*metabolism
MH  - YAP-Signaling Proteins
MH  - beta Catenin/genetics/metabolism
PMC - PMC3133743
MID - NIHMS295307
EDAT- 2011/04/23 06:00
MHDA- 2011/05/06 06:00
PMCR- 2012/04/22
CRDT- 2011/04/23 06:00
PHST- 2011/04/23 06:00 [entrez]
PHST- 2011/04/23 06:00 [pubmed]
PHST- 2011/05/06 06:00 [medline]
PHST- 2012/04/22 00:00 [pmc-release]
AID - 332/6028/458 [pii]
AID - 10.1126/science.1199010 [doi]
PST - ppublish
SO  - Science. 2011 Apr 22;332(6028):458-61. doi: 10.1126/science.1199010.