Canonical Wnt signaling functions in second heart field to promote right ventricular growth

doi:10.1073/pnas.0701212104

Canonical Wnt signaling functions in second heart field to promote right ventricular growth

*Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030;
^†Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Unit 1000, 1515 Holcombe Boulevard, Houston, TX 77030;
^‡Training Program in Genes and Development, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77225; and
^§Program in Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030

Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved April 13, 2007 (received for review February 9, 2007)

Abstract

The second heart field (SHF), progenitor cells that are initially sequestered outside the heart, migrates into the heart and gives rise to endocardium, myocardium, and smooth muscle. Because of its distinct developmental history, the SHF is likely subjected to different signals from that of the first heart field. Previous experiments revealed that canonical Wnt signaling negatively regulated first heart field specification. We inactivated the obligate canonical Wnt effector β-catenin using a β-catenin conditional null allele and the Mef2c AHF cre driver that directs cre activity specifically in SHF. We also expressed a stabilized form of β-catenin to model continuous Wnt signaling in SHF. Our data indicate that Wnt signaling acts in a positive fashion to promote right ventricular and interventricular myocardial expansion. Cyclin D2 and Tgfβ2 expression was drastically reduced in β-catenin loss-of-function mutants, indicating that Wnt signaling is required for patterning and expansion of SHF derivatives. Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium.

Footnotes

^¶To whom correspondence should be addressed. E-mail: jmartin{at}ibt.tamhsc.edu
Author contributions: J.F.M. designed research; D.A., X.F., J.W., M.-F.L., and L.C. performed research; A.B. and W.H.K. contributed new reagents/analytic tools; D.A. and J.F.M. analyzed data; and D.A. and J.F.M. 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/0701212104/DC1.
Abbreviations:

FHF,

first heart field;

SHF,

second heart field;

OFT,

outflow tract;

RV,

right ventricle;

CNC,

cardiac neural crest;

dpc,

days postcoitum.