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Developmental Regulation and Function of Thyroid Hormone Receptors and 9-cis Retinoic Acid Receptors during Xenopus tropicalis Metamorphosis

Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, Program on Cell Regulation and Metabolism, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Yun-Bo Shi, Laboratory of Gene Regulation and Development, Building 18 T, Room 106, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. E-mail: shi{at}helix.nih.gov.

Amphibian metamorphosis serves as an excellent model to study T₃ function during postembryonic development in vertebrate due to its total dependence on T₃. Earlier molecular studies in the model species Xenopus laevis have led to a number of important in vivo findings on the function and mechanisms of T₃ receptor (TR) action during vertebrate development. However, the lack of genomic sequence information, its tetraploid genome, and lengthy developmental cycle hinder further analyses on TR functions. In this regard, the highly related species, Xenopus tropicalis, is much more advantageous. Toward developing X. tropicalis for genome-wide and genetic studies of TR function, we analyzed the expression profiles of TRs and their heterodimerization partners, retinoid X receptors (RXRs) or 9-cis retinoic acid receptors. We show that their expression correlates with transformations in different organs and that TR/RXR heterodimers are capable of repressing and activating gene expression in vivo in the absence and presence of T₃, respectively. We further demonstrate that TRs are bound to endogenous target genes in X. tropicalis tadpoles. Our results thus support a role of TRs in mediating the metamorphic effects of T₃ in X. tropicalis. More importantly, the similarities in the expression and function between X. tropicalis and X. laevis TRs and RXRs as demonstrated by our study also pave the way to take advantages of existing morphological, molecular, and cellular knowledge of X. laevis development and the genetic and sequence superiority of X. tropicalis to dissect the molecular pathways governing tissue/organ-specific transformations during vertebrate postembryonic development.

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				H. Matsuda, B. D. Paul, C. Y. Choi, T. Hasebe, and Y.-B. Shi Novel Functions of Protein Arginine Methyltransferase 1 in Thyroid Hormone Receptor-Mediated Transcription and in the Regulation of Metamorphic Rate in Xenopus laevis Mol. Cell. Biol., February 1, 2009; 29(3): 745 - 757. [Abstract] [Full Text] [PDF]