Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis.
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.
Lin
Lizhu
L
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cui
Li
L
Zhou
Wenlai
W
Dufort
Daniel
D
Zhang
Xiaoxue
X
Cai
Chen-Leng
CL
Bu
Lei
L
Yang
Lei
L
Martin
Jody
J
Kemler
Rolf
R
Rosenfeld
Michael G
MG
Chen
Ju
J
Evans
Sylvia M
SM
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002319:Cardiovascular System / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D010609:Pharyngeal Muscles / Q000098:blood supply / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D051176:beta Catenin; C063843:insulin gene enhancer binding protein Isl-1