UP-REGULATION OF AP-2 IN THE SKIN OF XENOPUS-LAEVIS DURING THYROID HORMONE-INDUCED METAMORPHOSIS

During amphibian metamorphosis dramatic changes occur in the morphogen esis and differentiation of the epidermis. Concurrently with these cha nges, the 63 kDa keratin gene is upregulated from low basal levels to high levels. What makes these processes unique is that they are contro lled by triiodothyronine (T-3) and can be duplicated in cultures of pu rified epidermal cells. Since there is a 2 day lag period between the addition of T-3 and the upregulation of keratin gene expression and te rminal differentiation, recent studies have focused on identifying the genes activated during the lag period. We assume that the transcripti on factors required for upregulation of the keratin gene are induced b y T-3 during the lag period, and therefore we have cloned the keratin gene so that promoter analyses can be conducted. S1 mapping assays hav e shown that the same transcription start sites are used during premet amorphosis when the keratin gene is basally expressed, during metamorp hosis when it is T-3-upregulated, and in the adult epidermis where it is expressed independently of T-3. During the early part of the lag pe riod TRP and AP-2 mRNA levels are upregulated in the epidermis by T-3. The transcription factor AP-2 is expressed at high levels in the skin of premetamorphic larvae and induced about fivefold by T-3 but is not induced in an epithelial cell line (XL-177). Since the keratin mRNA, AP-2 mRNA, and other genes induced during the lag period ore expressed in premetamorphic larvae it appears that T-3 functions by upregulatin g the expression of genes previously activated by a T-3-independent pr ocess. This preprogramming may account for the tissue specificity of T -3 action during metamorphosis. (C) 1994 Wiley-Liss, Inc.