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Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature
Author(s) -
Wang Suya,
Huang Weiliang,
Castillo Hozana A.,
Kane Maureen A.,
XavierNeto José,
Trainor Paul A.,
Moise Alexander R.
Publication year - 2018
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24639
Subject(s) - retinoic acid , biology , heart development , paracrine signalling , microbiology and biotechnology , embryonic heart , embryonic stem cell , signal transduction , medicine , endocrinology , receptor , genetics , cell culture , gene
Background : During the final stages of heart development the myocardium grows and becomes vascularized by means of paracrine factors and cell progenitors derived from the epicardium. There is evidence to suggest that retinoic acid (RA), a metabolite of vitamin A, plays an important role in epicardial‐based developmental programming. However, the consequences of altered RA‐signaling in coronary development have not been systematically investigated. Results: We explored the developmental consequences of altered RA‐signaling in late cardiogenic events that involve the epicardium. For this, we used a model of embryonic RA excess based on mouse embryos deficient in the retinaldehyde reductase DHRS3, and a complementary model of embryonic RA deficiency based on pharmacological inhibition of RA synthesis. We found that alterations in embryonic RA signaling led to a thin myocardium and aberrant coronary vessel formation and remodeling. Both excess, and deficient RA‐signaling are associated with reductions in ventricular coverage and density of coronary vessels, altered vessel morphology, and impaired recruitment of epicardial‐derived mural cells. Using a combined transcriptome and proteome profiling approach, we found that RA treatment of epicardial cells influenced key signaling pathways relevant for cardiac development. Conclusions: Epicardial RA‐signaling plays critical roles in the development of the coronary vasculature needed to support myocardial growth. Developmental Dynamics 247:976‐991, 2018 . © 2018 Wiley Periodicals, Inc.