Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 47, Pages 18531-18536Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703113104
Keywords
BmpR1a; first heart field; heart looping; mesoderm patterning; second heart field
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Heart formation requires the coordinated recruitment of multiple cardiac progenitor cell populations derived from both the first and second heart fields. In this study, we have ablated the Bmp receptor 1 a and the Writ effector beta-catenin in the developing heart of mice by using MesP1-cre, which acts in early mesoderm progenitors that contribute to both first and second heart fields. Remarkably, the entire cardiac crescent and later the primitive ventricle were absent in MesP1-cre, BmpR1a(lox/lox) mutants. Although myocardial progenitor markers such as Nkx2-5 and Isl1 and the differentiation marker MLC2a were detected in the small, remaining cardiac field in these mutants, the first heart field markers, eHand and Tbx-5, were not expressed. We conclude from these results that Bmp receptor signaling is crucial for the specification of the first heart field. In MesP1-cre, beta-catenin(lox/lox) mutants, cardiac crescent formation, as well as first heart field markers,were not affected, although cardiac looping and right ventricle formation were blocked. Expression of Isl1 and Bmp4 in second heart field progenitors was strongly reduced. In contrast, in a gain-of-function mutation of beta-catenin using MesP1-cre, we revealed an expansion of Isl1 and Bmp4 expressing cells, although the heart tube was not formed. We conclude from these results that Wnt/beta-catenin signaling regulates second heart-field development, and that a precise amount and/or timing of Wnt/beta-catenin signaling is required for proper heart tube formation and cardiac looping.
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