Retionic acid and its receptors are required for expression of aryl hydrocarbon receptor mRNA and embryonic development of blood vessel and bone in the medaka fish, Oryzias latipes

Retinoic acid (RA), the active derivative of vitamin A, is essential for normal embryonic development of vertebrates because both the lack and excess of RA result in developmental malformations. We previously reported that aryl hydrocarbon receptor (AHR) is also required for vascular and bone formation by regulating cytochrome P450 expression. However, little is known about the roles of retinoic acid receptors (RAR) and retinoid X receptors (RXR) in the embryonic development of blood vessels and molecular cross-talk between RAR/RXR and AHR. We report for the first time that RA and RAR/RXR are required for expression of AHR mRNA and the embryonic development of blood vessel and bone. The embryonic organogenesis of medaka fish was specifically inhibited by an inhibitor of RA synthesis (diethylaminobenzaldehyde), antagonists of RAR (Ro41-5253) and RXR (Ro71-4595), agonist (beta-naphthoflavone) and antagonist (alpha-naphthoflavone) of AHR, and excess RA. These reagents are useful for future studies to elucidate molecular mechanisms for vascular and bone formation in the medaka embryogenesis. Our results also show that medaka embryos may be useful for screening inhibitors of vascular formation for anti-cancer drugs.