title: All-trans 3,4-didehydroretinoic acid equals all-trans retinoic acid in support of chick neuronal development.
abstract: All-trans 3,4-didehydroretinoic acid (at-ddRA) has been identified as a biologically important retinoid in avian, but not mammalian, embryonic development. In this report, we show that at-ddRA, like all-trans retinoic acid (atRA), supports the survival and differentiation of sympathetic neurons of the embryonic chick. Furthermore, the expression of the retinoid-responsive gene RARbeta2 is increased in neurons exposed to either at-ddRA or atRA. The mechanism whereby at-ddRA exerts its effects in chick neurons may involve binding to and activation of nuclear retinoid receptors. For this reason, the binding of recombinant chick RARbeta2 to at-ddRA and to receptor-specific DNA response elements was examined and compared with the binding characteristics of recombinant murine RARbeta2. The chick RARbeta2, like the mammalian RAR, binds to [3H]atRA with high affinity (Kd=0.7-2 nM). Furthermore, both chick and murine RARbeta2 bind equally well to at-ddRA, atRA, and 9-cis RA, but neither receptor shows appreciable binding to 13-cis RA. The chick RARbeta2 recognizes previously described retinoic acid response elements of mammalian gene promoters and, like mammalian RARbeta2, shows enhanced binding in the presence of RXR. This study provides evidence that at-ddRA, like atRA, supports neuronal development in the chick by its interaction with nuclear retinoid receptors.
authors.affiliation: Interdepartmental Graduate Program in Nutrional Sciences, School of Pharmacy, University of Wisconsin-Madison, 53706, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Repa
authors.forename: L A
authors.initials: LA
authors.lastname: Plum
authors.forename: P K
authors.initials: PK
authors.lastname: Tadikonda
authors.forename: M
authors.initials: M
authors.lastname: Clagett-Dame
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000196:embryology; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; C082925:retinoic acid receptor beta; C064742:3,4-didehydroretinoic acid; D014212:Tretinoin