Seleiro, Eduardo Augusto Pombo; (1994) Study of the expression of two RXR genes in the chicken. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The retinoid X receptors (RXRs), together with the retinoic acid receptors (RARs), have important roles in mediating the effects of retinoids during development and differentiation. They are ligand-dependent transcription factors belonging to the steroid/thyroid hormone receptor superfamily. The RXRs have been shown to activate the expression of target genes in the presence of their ligand 9-cis-retinoic acid, but their main function seems to be as auxiliary proteins, that form heterodimers with other members of the superfamily, and enhance their DNA-binding and transcriptional activities. In this work, the expression of two RXR genes in the chicken was characterised: The chicken RXRγ gene was shown to give rise to two major mRNA species of different sizes (RXRγ1 and RXRγ2), that have a tissue specific distribution in embryonic and adult tissues: RXRγ1 is expressed predominantly in the eye, and is also expressed at lower levels in some neural crest derived tissues, such as the peripheral nervous system and the adrenal glands; RXRγ2 is expressed exclusively in the liver. The major sites of expression of the chicken RXRγ gene both in the embryo and in the adult are the retina and the liver, suggesting a possible involvement of this gene in the metabolism of vitamin A. Ribonuclease protection analysis of these two distinct chicken RXRγ mRNAs, following the isolation of the corresponding cDNA clones, showed that they differed from each other in their 5' regions, and have the potential to encode two distinct protein isoforms of RXRγ that, like the RAR isoforms, differ only in their amino-terminal A domains. Examination of a genomic clone for chicken RXRγ, suggested that the two RNA isoforms may be generated by the use of alternative promoters. A cDNA clone for chicken RXRα was also isolated. Preliminary analysis of the expression pattern of the chicken RXRα gene, showed that a single major transcript of this gene is found in most embryonic and adult tissues, with only slight variations in its levels of expression in different tissues. In particular this gene is expressed in the limb buds, at the stages when the patterning events are occuring, make it a possible candidate for mediating the proposed effects of 9c-RA as a positional signalling molecule.

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