title: Mesenchymal/epithelial regulation of retinoic acid signaling in the olfactory placode.
abstract: We asked whether mesenchymal/epithelial (M/E) interactions regulate retinoic acid (RA) signaling in the olfactory placode and whether this regulation is similar to that at other sites of induction, including the limbs, branchial arches, and heart. RA is produced by the mesenchyme at all sites, and subsets of mesenchymal cells express the RA synthetic enzyme RALDH2, independent of M/E interactions. In the placode, RA-producing mesenchyme is further distinguished by its coincidence with a molecularly distinct population of neural crest-associated cells. At all sites, expression of additional RA signaling molecules (RARalpha, RARbeta, RXR, CRABP1) depends on M/E interactions. Of these molecules, RA regulates only RARbeta, and this regulation depends on M/E interaction. Expression of Fgf8, shh, and Bmp4, all of which are thought to influence RA signaling, is also regulated by M/E interactions independent of RA at all sites. Despite these common features, RALDH3 expression is distinct in the placode, as is regulation of RARbeta and RALDH2 by Fgf8. Thus, M/E interactions regulate expression of RA receptors and cofactors in the olfactory placode and other inductive sites. Some aspects of regulation in the placode are distinct, perhaps reflecting unique roles for additional local signals in neuronal differentiation in the developing olfactory pathway.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bhasin
authors.forename: T M
authors.initials: TM
authors.lastname: Maynard
authors.forename: P A
authors.initials: PA
authors.lastname: Gallagher
authors.forename: A-S
authors.initials: AS
authors.lastname: LaMantia
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics; D000818:Animals; D046508:Culture Techniques; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology / Q000502:physiology; D009833:Olfactory Pathways / Q000196:embryology* / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000235:genetics; D015398:Signal Transduction; D014212:Tretinoin / Q000502:physiology*
chemical_list: C496457:Fgf8 protein, mouse; D018168:Receptors, Retinoic Acid; D051524:Fibroblast Growth Factor 8; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse