Abstract
Retinoic acid (RA), a derivative of vitamin A, is involved in signal transduction during vertebrate organogenesis. Retinoids through binding to nuclear receptors called RA receptors (RARs) and retinoid X receptors (RXRs) regulate various processes during cardiogenesis. Deregulated retinoid signaling thus has later consequences leading to cardiac malformations. In this review, we will summarize and discuss our current knowledge on the role of RA signaling during heart development, especially during patterning of the heart fields. We have also integrated recent experiments essential for our understanding of the role of RA signaling during epicardial development and myocardial growth.
Highlights
In vertebrates, the heart is one of the first organs to acquire its function, and continuous pump function is essential for distribution of oxygen and nutrients during fetal and post-natal life [1]
Since the first experimental data demonstrating the relationship between maternal vitamin A deficiency and congenital heart defects, there have been major advances in our understanding of the role of Retinoic acid (RA)
The action of RA signaling on cardiac progenitor cells has gained renewed interpretation with the identification of the second heart field (SHF)
Summary
The heart is one of the first organs to acquire its function, and continuous pump function is essential for distribution of oxygen and nutrients during fetal and post-natal life [1]. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function [19,23,24,25,26,27] These studies demonstrated that RA synthesis during critical processes of heart development is controlled largely by retinaldehyde dehydrogenase 2 (RALDH2). We focus on our recent work demonstrating that early expression of RA is required to regulate the anteroposterior expression of Hox genes in a cardiac progenitor cell population termed the second heart field. This population of cardiac progenitor cells contributes to major components of the heart including outflow tract, right ventricular and atrial myocardium [2]. AA, aortic arch; EPDCs, epicardium-derived cells; LA, left atrium; LV, left ventricle; OFT, outflow tract; PA, pharyngeal arch; PEO, pro-epicardial organ; PLA primitive left atrium; PRA, primitive right atrium; RA, right atrium; RV, right ventricle; Tr, trabeculae
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