Recent insights on the role and regulation of retinoic acid signaling during epicardial development

Genesis. 2019 Jul;57(7-8):e23303. doi: 10.1002/dvg.23303. Epub 2019 May 8.

Abstract

The vitamin A metabolite, retinoic acid, carries out essential and conserved roles in vertebrate heart development. Retinoic acid signals via retinoic acid receptors (RAR)/retinoid X receptors (RXRs) heterodimers to induce the expression of genes that control cell fate specification, proliferation, and differentiation. Alterations in retinoic acid levels are often associated with congenital heart defects. Therefore, embryonic levels of retinoic acid need to be carefully regulated through the activity of enzymes, binding proteins and transporters involved in vitamin A metabolism. Here, we review evidence of the complex mechanisms that control the fetal uptake and synthesis of retinoic acid from vitamin A precursors. Next, we highlight recent evidence of the role of retinoic acid in orchestrating myocardial compact zone growth and coronary vascular development.

Keywords: congenital heart defects; epicardium; heart development; retinoic acid; vitamin A.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental
  • Humans
  • Pericardium / embryology*
  • Pericardium / metabolism
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Signal Transduction*
  • Tretinoin / metabolism*

Substances

  • Receptors, Retinoic Acid
  • Tretinoin