Pitx2cpatterns anterior myocardium and aortic arch vessels and is required for local cell movement into atrioventricular cushions
Author:
Liu Chengyu1, Liu Wei1, Palie Jennifer1, Lu Mei Fang1, Brown Nigel A.2, Martin James F.1
Affiliation:
1. Alkek Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 Holcombe Blvd, Houston, TX 77030, USA 2. Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, University of London, Cranmer Terrace, London SW17 ORE, UK
Abstract
Inactivation of the left-right asymmetry gene Pitx2 has been shown, in mice, to result in right isomerism with associated defects that are similar to that found in humans. We show that the Pitx2c isoform is expressed asymmetrically in a presumptive secondary heart field within the branchial arch and splanchnic mesoderm that contributes to the aortic sac and conotruncal myocardium. Pitx2c was expressed in left aortic sac mesothelium and in left splanchnic and branchial arch mesoderm near the junction of the aortic sac and branchial arch arteries. Mice with an isoform-specific deletion of Pitx2c had defects in asymmetric remodeling of the aortic arch vessels. Fatemapping studies using a Pitx2 cre recombinase knock-in allele showed that daughters ofPitx2-expressing cells populated the right and left ventricles,atrioventricular cushions and valves and pulmonary veins. In Pitx2mutant embryos, descendents of Pitx2-expressing cells failed to contribute to the atrioventricular cushions and valves and the pulmonary vein,resulting in abnormal morphogenesis of these structures. Our data provide functional evidence that the presumptive secondary heart field, derived from branchial arch and splanchnic mesoderm, patterns the forming outflow tract and reveal a role for Pitx2c in aortic arch remodeling. Moreover, our findings suggest that a major function of the Pitx2-mediated left right asymmetry pathway is to pattern the aortic arches, outflow tract and atrioventricular valves and cushions.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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