Thyroid Hormone Receptor Is Essential for Larval Epithelial Apoptosis and Adult Epithelial Stem Cell Development but Not Adult Intestinal Morphogenesis during Xenopus tropicalis Metamorphosis
Open Access
- 3 March 2021
- Vol. 10 (3), 536
- https://doi.org/10.3390/cells10030536
Abstract
Vertebrate postembryonic development is regulated by thyroid hormone (T3). Of particular interest is anuran metamorphosis, which offers several unique advantages for studying the role of T3 and its two nuclear receptor genes, TRα and TRβ, during postembryonic development. We have recently generated TR double knockout (TRDKO) Xenopus tropicalis animals and reported that TR is essential for the completion of metamorphosis. Furthermore, TRDKO tadpoles are stalled at the climax of metamorphosis before eventual death. Here we show that TRDKO intestine lacked larval epithelial cell death and adult stem cell formation/proliferation during natural metamorphosis. Interestingly, TRDKO tadpole intestine had premature formation of adult-like epithelial folds and muscle development. In addition, T3 treatment of premetamorphic TRDKO tadpoles failed to induce any metamorphic changes in the intestine. Furthermore, RNA-seq analysis revealed that TRDKO altered the expression of many genes in biological pathways such as Wnt signaling and the cell cycle that likely underlay the inhibition of larval epithelial cell death and adult stem cell development caused by removing both TR genes. Our data suggest that liganded TR is required for larval epithelial cell degeneration and adult stem cell formation, whereas unliganded TR prevents precocious adult tissue morphogenesis such as smooth-muscle development and epithelial folding.Keywords
Funding Information
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (Intramural research)
- Japan Society for the Promotion of Science (postdoctoral fellowship)
This publication has 79 references indexed in Scilit:
- Pathview: an R/Bioconductor package for pathway-based data integration and visualizationBioinformatics, 2013
- RNA-Seq analysis in MeVBioinformatics, 2011
- Blimp1 regulates the transition of neonatal to adult intestinal epitheliumNature Communications, 2011
- The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytesProceedings of the National Academy of Sciences of the United States of America, 2011
- An Essential and Evolutionarily Conserved Role of Protein Arginine Methyltransferase 1 for Adult Intestinal Stem Cells During Postembryonic DevelopmentThe International Journal of Cell Cloning, 2010
- Dual Functions of Thyroid Hormone Receptors in Vertebrate Development: The Roles of Histone-Modifying Cofactor ComplexesThyroid®, 2009
- Cell–cell interactions during remodeling of the intestine at metamorphosis in Xenopus laevisDevelopmental Biology, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- Amphibian metamorphosisDevelopmental Biology, 2007
- Matrix metalloproteinases and the regulation of tissue remodellingNature Reviews Molecular Cell Biology, 2007