title: Expression of a retinoic acid response element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis.
abstract: Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improved considerably with the identification of nuclear receptors for RA (RARs) and RA-responsive genes, the exact relationship between the proposed morphogenetic activity of RA and its teratogenic effects remains to be characterized. Here, we show that a RA response element (RARE) present in the RAR beta gene can direct specific spatial and temporal expression of an hsplacZ transgene during mouse embryogenesis. In the early embryo, the transgene is expressed in a specific anterior-posterior domain that is completely obliterated by treatment of pregnant mice with teratogenic doses of RA. The expression of the transgene becomes more restricted as organogenesis progresses and mimics closely the reported expression of the RAR beta gene. These results suggest that, in vivo, some of the morphogenetic effects of RA could be mediated through localized transcriptional activity controlled by the various RARs. The specific pattern of expression of the RAREhsplacZ transgene does not correlate with the proposed sites of action of RA as defined by its teratogenic effects but does support a role for RA in early anterior-posterior patterning along the body axis.
authors.affiliation: Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Rossant
authors.forename: R
authors.initials: R
authors.lastname: Zirngibl
authors.forename: D
authors.initials: D
authors.lastname: Cado
authors.forename: M
authors.initials: M
authors.lastname: Shago
authors.forename: V
authors.initials: V
authors.lastname: Giguère
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D005822:Genetic Vectors; D006360:Heat-Shock Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000187:drug effects; D011247:Pregnancy; D016385:TATA Box; D013723:Teratogens; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000633:toxicity*; D001616:beta-Galactosidase / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; D013723:Teratogens; D014212:Tretinoin; D001616:beta-Galactosidase