β-Catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis

doi:10.1073/pnas.0700923104

β-Catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis

*Skaggs School of Pharmacy and Pharmaceutical Sciences,
^†Howard Hughes Medical Institute and Department of Medicine, and
^¶School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093;
^‡Department of Obstetrics and Gynecology, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1; and
^§Max-Planck-Institute of Immunobiology, Stubeweg 51, 79108 Freiburg, Germany

Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved April 13, 2007 (received for review February 1, 2007)

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 β-catenin is required for Isl1 expression in cardiac progenitors, directly regulating the Isl1 promoter. Ablation of β-catenin in Isl1-expressing progenitors disrupts multiple aspects of cardiogenesis, resulting in embryonic lethality at E13. β-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 β-catenin signaling regulates proliferation and survival of cardiac progenitors.

Footnotes

^‖To whom correspondence should be addressed. E-mail: syevans{at}ucsd.edu
Author contributions: L.C. and W.Z. contributed equally to this work; L.L. and S.M.E. designed research; L.L., L.C., W.Z., X.Z., L.B., L.Y., and J.M. performed research; D.D., C.-L.C., and R.K. contributed new reagents/analytic tools; L.L., M.G.R., J.C., and S.M.E. analyzed data; and L.L. and S.M.E. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700923104/DC1.
Abbreviations:

En,

embryonic day;

PAA,

pharyngeal arch artery;

TCF,

T cell factor.