TEMPORAL AND SPATIAL REGULATION OF A PUTATIVE TRANSCRIPTIONAL REPRESSOR IMPLICATES IT AS PLAYING A ROLE IN THYROID HORMONE-DEPENDENT ORGAN TRANSFORMATION

Thyroid hormone (T-3) induces both larval cell death and adult cell pr oliferation and differentiation during amphibian metamorphosis. We hav e previously isolated a bZip transcription factor (TH/bZip) as a T-3 r esponse gene in the metamorphosing Xenopus intestine. We demonstrate t hat the Xenopus TH/bZip gene is a direct T-3-response gene and ubiquit ously regulated by T-3 in tadpoles. Developmental in situ hybridizatio n analyses have shown that TH/bZip gene is regulated in a cell-type-sp ecific manner that correlates with tissue transformation. In particula r, it is found to be expressed in the larval intestinal epithelial ce Is prior to their apoptotic degeneration and in the proliferating adul t cell types. However, the gene is repressed again upon adult cell dif ferentiation. This regulation pattern mimics that of the thyroid hormo ne receptor (TR)beta genes. Since the TH/bZip gene is a direct T-3-res ponse gene, such a correlation suggests that TR beta may be involved i n the regulation of the TH/bZip gene. More importantly, in situ hybrid ization reveals a strong spatiotemporal correlation of TH/bZip express ion with the tissue-specific remodeling in the intestine, suggesting t hat TH/bZip gene may participate, depending on the cell types, in both inducing apoptosis and stimulating cell proliferation. A similar role has been reported For the proto-oncogene c-myc, another leucine-zippe r-containing transcription factor, in tissue culture cell systems. (C) 1997 Wiley-Liss, Inc.