The research in the Unit of Molecular Morphogenesis is focussed on the understanding of the molecular mechanism of amphibian metamorphosis. The control of this developmental process by thyroid hormone (TH) offers a unique paradigm in which to study genes that are important for post- embryonic organ development. We began to study metamorphosis by choosing the remodeling of the tadpole intestine in Xenopus laevis as a model system. The tadpole intestine is a simple tubular structure consisting of primarily a single layer of primary epithelial cells. During metamorphosis, it is transformed into a multiply folded adult epithelium with elaborate connective tussue and muscles through specific cell death and selective all proliferation and differentiation. We have isolated and identified many TH-response genes in the intestine during this transition. Among them are the TH receptor (TR) beta genes. Analysis of the receptor gene expression in different tissues shows that not only TRbeta but also TRalpha and RXR genes are regulated in an organ-dependent manner during metamorphosis. RXRs are known to be able to form heterodimers with TRs. Indeed, Xenopus TR/RXR heterodimers can bind to their binding site even in a chromatinized template and activate or repress transcription in the presence or absence of TH, respectively. Thus, our results strongly suggest TR/RXR heterodimer are the functional complexes mediating the effect of TH during metamorphosis. In addition, we have also obtained evidence that two NFI genes, which are also regulated by TH, are involved in the adult organ development. Finally, a putative morphogen, hedgehog, and the matrix metalloproteinase, stromelysin-3, appear to participate in the regulation of cell-cell and cell-ECM interactions during intestinal remodeling.
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