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 many TH-response genes in the intestine during this transition. Among them are genes encoding matrix metalloproteinases (MMPs) and a putative morphogen, the Xenopus hedgehog. Thus, a major area of our work is to understand how these extracellular proteins influence organogenesis. Our evidence suggests that the Xenopus hedgehog functions in initiating and/or stimulating adult intestinal epithelial all proliferation and differentiation, in agreement with its morphogenic roles in other species. On the other hand, MMPs appear to be involved in ECM remodeling, which in turn influences cell behavior, especially larval epithelial apoptosis and adult cell proliferation. We have developed in vitro cell and organ culture systems which will allow us to further investigate how these proteins function to regulate cell-cell and cell-ECM interactions. The second research area aims at investigating the function of thyroid hormone receptors (TRs) during metamorphosis. Our current work has demonstrated that TR/RXR (9-cis retinoic acid receptor) can function within a chromatin context and that transcriptional activation leads to chromatin disruption. We have revealed a number of interesting characteristic associated with TR function. In addition, we have identified and functionally characterized a mutant TR in Xenopus laevis.
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