Abstract
Recent studies have demonstrated that the LIM homeodomain transcription factor Islet1 (Isl1) marks pluripotent cardiovascular progenitor cells and is required for proliferation, survival, and migration of recently defined second heart field progenitors. Factors that are upstream of Isl1 in cardiovascular progenitors have not yet been defined. Here we demonstrate that beta-catenin is required for Isl1 expression in cardiac progenitors, directly regulating the Isl1 promoter. Ablation of beta-catenin in Isl1-expressing progenitors disrupts multiple aspects of cardiogenesis, resulting in embryonic lethality at E13. beta-Catenin is also required upstream of a number of genes required for pharyngeal arch, outflow tract, and/or atrial septal morphogenesis, including Tbx2, Tbx3, Wnt11, Shh, and Pitx2. Our findings demonstrate that beta-catenin signaling regulates proliferation and survival of cardiac progenitors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Base Sequence
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Cardiovascular System / cytology*
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Cardiovascular System / metabolism*
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Cell Differentiation
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Cell Movement
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Cell Proliferation
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Embryo, Mammalian / cytology
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Embryo, Mammalian / embryology
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Embryo, Mammalian / metabolism
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Gene Expression Regulation, Developmental
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Heart / embryology*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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LIM-Homeodomain Proteins
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Mutation / genetics
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Myocardium / cytology*
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Myocardium / metabolism*
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Pharyngeal Muscles / blood supply
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Pharyngeal Muscles / embryology
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Pharyngeal Muscles / metabolism
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Stem Cells / cytology
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Stem Cells / metabolism
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Time Factors
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Transcription Factors
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beta Catenin / deficiency
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Homeodomain Proteins
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LIM-Homeodomain Proteins
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Transcription Factors
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beta Catenin
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insulin gene enhancer binding protein Isl-1