Temporal and spatial regulation of a putative transcriptional repressor implicates it as playing a role in thyroid hormone-dependent organ transformation.

Thyroid hormone (T3) induces both larval cell death and adult cell proliferation and differentiation during amphibian metamorphosis. We have previously isolated a bZip transcription factor (TH/bZip) as a T3 response gene in the metamorphosing Xenopus intestine. We demonstrate that the Xenopus TH/bZip gene is a direct T3-response gene and ubiquitously regulated by T3 in tadpoles. Developmental in situ hybridization analyses have shown that TH/bZip gene is regulated in a cell-type-specific manner that correlates with tissue transformation. In particular, it is found to be expressed in the larval intestinal epithelial cells prior to their apoptotic degeneration and in the proliferating adult cell types. However, the gene is repressed again upon adult cell differentiation. This regulation pattern mimics that of the thyroid hormone receptor (TR)beta genes. Since the TH/bZip gene is a direct T3-response gene, such a correlation suggests that TR beta may be involved in the regulation of the TH/bZip gene. More importantly, in situ hybridization reveals a strong spatiotemporal correlation of TH/bZip expression with the tissue-specific remodeling in the intestine, suggesting that 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-zipper-containing transcription factor, in tissue culture cell systems.