title: Molecular and cytological analyses reveal distinct transformations of intestinal epithelial cells during Xenopus metamorphosis.
abstract: BACKGROUND
  The thyroid hormone (T3)-induced formation of adult intestine during amphibian metamorphosis resembles the maturation of the mammalian intestine during postembryonic development, the period around birth when plasma T3 level peaks. This process involves de novo formation of adult intestinal stem cells as well as the removal of the larval epithelial cells through apoptosis. Earlier studies have revealed a number of cytological and molecular markers for the epithelial cells undergoing different changes during metamorphosis. However, the lack of established double labeling has made it difficult to ascertain the identities of the metamorphosing epithelial cells.
  
  
  RESULTS
  Here, we carried out different double-staining with a number of cytological and molecular markers during T3-induced and natural metamorphosis in Xenopus laevis. Our studies demonstrated conclusively that the clusters of proliferating cells in the epithelium at the climax of metamorphosis are undifferentiated epithelial cells and express the well-known adult intestinal stem cell marker gene Lgr5. We further show that the adult stem cells and apoptotic larval epithelial cells are distinct epithelial cells during metamorphosis.
  
  
  CONCLUSIONS
  Our findings suggest that morphologically identical larval epithelial cells choose two alternative paths: programmed cell death or dedifferentiation to form adult stem cells, in response to T3 during metamorphosis with apoptosis occurring prior to the formation of the proliferating adult stem cell clusters (islets).
authors.affiliation: Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., Bethesda, MD 20892 USA.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Okada
authors.affiliation: Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., Bethesda, MD 20892 USA.
authors.forename: Luan
authors.initials: L
authors.lastname: Wen
authors.affiliation: Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., Bethesda, MD 20892 USA.|Meso-Scale Discovery, Rockville, MD USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Miller
authors.affiliation: Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., Bethesda, MD 20892 USA.|Oncology Department, Zhejiang Provincial People's Hospital, Hangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr., Bethesda, MD 20892 USA.
authors.forename: Yun-Bo
authors.initials: YB
authors.lastname: Shi
keywords: Intestine; Metamorphosis; Stem cells; Thyroid hormone; Thyroid hormone receptor; Xenopus laevis