Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times

Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested ev...

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Published in:Biochimica et biophysica acta 2015-02, Vol.1849 (2), p.94-111
Main Authors: Xavier-Neto, José, Sousa Costa, Ângela M., Figueira, Ana Carolina M., Caiaffa, Carlo Donato, Amaral, Fabio Neves do, Peres, Lara Maldanis Cerqueira, da Silva, Bárbara Santos Pires, Santos, Luana Nunes, Moise, Alexander R., Castillo, Hozana Andrade
Format: Article
Language:English
Subjects:
ALDH1A2
Animals
Biological Clocks - drug effects
Biological Clocks - physiology
Biological Evolution
Gene Expression Regulation, Developmental
Heart - drug effects
Heart - embryology
Heart - growth & development
Heart development
Humans
RAR
Receptors, Retinoic Acid - physiology
Retinoic acid
RXR
Signal Transduction - drug effects
Signal Transduction - genetics
Time Factors
Tretinoin - pharmacology
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Summary:Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development. •Retinoic acid (RA) signaling is an ancestral feature of bilaterian animals.•RA plays time-sensitive, sequential and multifaceted roles in cardiac development.•Bona fide RA gradients have been recently objectively demonstrated.•RA signaling is regulated by a balance between RA synthesis and degradation.•RA roles in early zebrafish cardiac development remain controversial.
ISSN:1874-9399
0006-3002
1876-4320
1878-2434
DOI:10.1016/j.bbagrm.2014.08.003