title: Function of RARgamma and RARalpha2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis.
abstract: Avian embryogenesis requires retinoid receptor activation by the vitamin A active form, retinoic acid (RA), during neurulation. We conducted loss-of-function analysis in quail embryos by nutritional deprivation of RA and by blocking generation of retinoid receptors. Here we identify a distinct role for RARalpha2 in cardiac inflow tract morphogenesis and for RARgamma in cardiac left/right orientation and looping morphogenesis. Blocking normal embryos with antisense oligonucleotides to RARalpha2 or RXRalpha diminishes GATA-4 transcripts, while blocking RARgamma or RXRalpha diminishes nodal and Pitx2 transcripts; the expression of these genes in the heart forming region resembles that of the vitamin A-deficient embryo. Blocking the function of RARgamma, RARalpha2, and RXRalpha recapitulates the complete vitamin A-deficient phenotype. RARgamma is the most potent mediator of the retinoid signal at this time of development. Our studies provide strong evidence that critical RA-requiring developmental events in the early avian embryo are regulated by means of distinct retinoid receptor signaling pathways.
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Romeih
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Michaille
authors.forename: Weihong
authors.initials: W
authors.lastname: Jiang
authors.forename: Maija H
authors.initials: MH
authors.lastname: Zile
mesh_terms: D000818:Animals; D002470:Cell Survival; D003370:Coturnix; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D050991:GATA4 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D009206:Myocardium / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D000097577:Homeobox Protein PITX2; D000097768:Retinoic Acid Receptor gamma
chemical_list: D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D018398:Homeodomain Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human