Retinoic acid signaling in vascular development

Abstract

Formation of the vasculature is an essential developmental process, delivering oxygen and nutrients to support cellular processes needed for tissue growth and maturation. Retinoic acid (RA) and its downstream signaling pathway is vital for normal pre- and post-natal development, playing key roles in the specification and formation of many organs and tissues. Here we review the role of RA in blood and lymph vascular development, beginning with embryonic yolk sac vasculogenesis and remodeling and discussing RA’s organ-specific roles in angiogenesis and vessel maturation. In particular, we highlight the multi-faceted role of RA signaling in CNS vascular development and acquisition of blood-brain barrier properties.

Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway

“…Retinoic acid (RA) can stimulate SMC migration and proliferation in the DA. Reviewing its function in development, the RA signaling pathway plays a role in developing several organs and tissues, such as the body axis, limbs, spinal cord, eye, heart, vasculature, and the reproductive tract [ 55 , 56 ]. As an active metabolite of vitamin A, there are several isoforms of RA, including all-trans retinoic acid (atRA), 9-cis-RA, and 13-cis-RA.…”

Retinoic Acid: A Key Regulator of Lung Development

“…RA is a key regulator of cellular growth, proliferation, differentiation, and embryogenesis per se, and one cannot discard that it may contribute to this phase of lung morphogenesis. For instance, retinoic acid is a major regulator of angiogenesis and vasculogenesis [85], and the organization of the pulmonary vascular bed initiates during the canalicular period. Therefore, RA may be involved in the development of the lung vascular system (please refer to Section 3.6).…”

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

“…These include RA-inducible factor FGF9, which indirectly supports coronary development through promoting cardiomyocyte proliferation and myocardial expression of VEGF (Lavine et al, 2006). Therefore, the effect of altered RA-signaling on coronary development in vivo is likely to reflect the aggregated impact of altered RA on myocardial expansion, vascular development and fetal erythropoiesis (Bohnsack, Lai, Dolle, & Hirschi, 2004;Brade et al, 2011;Canete, Cano, Munoz-Chapuli, & Carmona, 2017;Chanda, Ditadi, Iscove, & Keller, 2013;Pawlikowski, Wragge, & Siegenthaler, 2019). APJ is specifically expressed in sinus venosus-derived coronary vessels, and APJ signalling via its alternate ligand, elabela, was required for their angiogenic sprouting (Chen et al, 2014;Sharma, Ho, et al, 2017).…”

“…APJ is specifically expressed in sinus venosus-derived coronary vessels, and APJ signalling via its alternate ligand, elabela, was required for their angiogenic sprouting (Chen et al, 2014;Sharma, Ho, et al, 2017). Therefore, the effect of altered RA-signaling on coronary development in vivo is likely to reflect the aggregated impact of altered RA on myocardial expansion, vascular development and fetal erythropoiesis (Bohnsack, Lai, Dolle, & Hirschi, 2004;Brade et al, 2011;Canete, Cano, Munoz-Chapuli, & Carmona, 2017;Chanda, Ditadi, Iscove, & Keller, 2013;Pawlikowski, Wragge, & Siegenthaler, 2019).…”