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Differential expression of components of the retinoic acid signaling pathway in the adult mouse olfactory epithelium.

ABSTRACT: Position within a tissue often correlates with cellular phenotype, for example, differential expression of odorant receptors and cell adhesion molecules across the olfactory mucosa (OM). The association between position and phenotype is often paralleled by gradations in the concentration of retinoic acid (RA), caused by differential expression of the RA synthetic enzymes, the retinaldehyde dehydrogenases (RALDH). We show here that RALDH-1, -2, and -3 are enriched in the sustentacular cells, deep fibroblasts of the lamina propria, and the superficial fibroblasts, respectively, of the ventral and lateral OM as compared to the dorsomedial OM. The shift from high to low expression of the RALDHs matches the boundary defined by the differential expression of OCAM/mamFasII. Further, we found that RA-binding proteins are expressed in the epithelium overlying the RALDH-3 expressing fibroblasts of the lamina propria. Both findings suggest that local alterations in RA concentration may be more important than a gradient of RA across the epithelial plane, per se. In addition, RALDH-3 is found in a small population of basal cells in the ventral and lateral epithelium, which expand and contribute to the neuronal lineage following MeBr lesion. Indeed, transduction with a retrovirus expressing a dominant negative form of retinoic acid receptor type alpha blocks the reappearance of mature, olfactory marker protein (OMP) (+) olfactory neurons as compared to empty vector. These results support the notion of a potential role for RA, both in maintaining the spatial organization of the normal olfactory epithelium and in reestablishing the neuronal population during regeneration after injury.

SUBMITTER: Peluso CE

PROVIDER: S-EPMC3887393 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Differential expression of components of the retinoic acid signaling pathway in the adult mouse olfactory epithelium.

Peluso Carolyn E CE Jang Woochan W Dräger Ursula C UC Schwob James E JE

The Journal of comparative neurology 20121101 16

Position within a tissue often correlates with cellular phenotype, for example, differential expression of odorant receptors and cell adhesion molecules across the olfactory mucosa (OM). The association between position and phenotype is often paralleled by gradations in the concentration of retinoic acid (RA), caused by differential expression of the RA synthetic enzymes, the retinaldehyde dehydrogenases (RALDH). We show here that RALDH-1, -2, and -3 are enriched in the sustentacular cells, deep ...[more]

PMID: 22522724

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Project description:BackgroundVitamin A is necessary for kidney development and has also been linked to regulation of solute and water homeostasis and to protection against kidney stone disease, infection, inflammation, and scarring. Most functions of vitamin A are mediated by its main active form, all-trans retinoic acid (tRA), which binds retinoic acid receptors (RARs) to modulate gene expression. We and others have recently reported that renal tRA/RAR activity is confined to the ureteric bud (UB) and collecting duct (CD) cell lineage, suggesting that endogenous tRA/RARs primarily act through regulating gene expression in these cells in embryonic and adult kidney, respectively.Methodology/principal findingsTo explore target genes of endogenous tRA/RARs, we employed the mIMCD-3 mouse inner medullary CD cell line, which is a model of CD principal cells and exhibits constitutive tRA/RAR activity as CD principal cells do in vivo. Combining antagonism of RARs, inhibition of tRA synthesis, exposure to exogenous tRA, and gene expression profiling techniques, we have identified 125 genes as candidate targets and validated 20 genes that were highly regulated (Dhrs3, Sprr1a, and Ppbp were the top three). Endogenous tRA/RARs were more important in maintaining, rather than suppressing, constitutive gene expression. Although many identified genes were expressed in UBs and/or CDs, their exact functions in this cell lineage are still poorly defined. Nevertheless, gene ontology analysis suggests that these genes are involved in kidney development, renal functioning, and regulation of tRA signaling.Conclusions/significanceA rigorous approach to defining target genes for endogenous tRA/RARs has been established. At the pan-genomic level, genes regulated by endogenous tRA/RARs in a CD cell line have been catalogued for the first time. Such a catalogue will guide further studies on molecular mediators of endogenous tRA/RARs during kidney development and in relation to renal defects associated with vitamin A deficiency.

Dataset Information

Differential expression of components of the retinoic acid signaling pathway in the adult mouse olfactory epithelium.

Publications

Differential expression of components of the retinoic acid signaling pathway in the adult mouse olfactory epithelium.

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