A beta 2RARE-LacZ transgene identifies retinoic acid-mediated transcriptional activation in distinct cutaneous sites.

Retinoic acid and its derivatives (retinoids) exert profound influences on epithelial growth differentiation in a variety of tissues, including the skin. How retinoic acid mediates these effects is not fully understood. The recent cloning of a series of nuclear receptors for retinoic acid (RARs) has demonstrated that these proteins can function as ligand-inducible transcriptional enhancing factors. Moreover, all receptors are members of the steroid/thyroid hormone multigene family. In vitro studies have demonstrated the expression of RAR alpha, RAR beta, and RAR gamma in various cell types found in the skin. While multiple isoforms exist for each of the three RARs, it is unclear where each of these receptors functions in vivo to mediate the tissue-specific effects of retinoic acid. As a first step in determining sites of retinoic acid-mediated transcriptional activation in the skin and its appendages, we developed a transgenic model in which the retinoic acid response element (RARE) of the RAR beta 2 isoform is linked to a beta-galactosidase reporter gene. Our observations consistently demonstrate that retinoic acid transcriptionally activates the beta 2RARE in distinct areas of the skin. Of interest, certain of these areas are known to contain stem cells. These data clearly demonstrate that this type of transgenic "reporter" model can be used to further define retinoic acid-regulated signal transduction pathways in the skin, as well as other complex tissues. Furthermore, these observations raise the possibility that transcriptional activation of RAR beta 2 may regulate the growth and differentiation programs of selected populations of stem cells in the skin and its appendages.