title: Thyroid hormone-regulated Wnt5a/Ror2 signaling is essential for dedifferentiation of larval epithelial cells into adult stem cells in the Xenopus laevis intestine.
abstract: OBJECTIVE
  Amphibian intestinal remodeling, where thyroid hormone (T3) induces some larval epithelial cells to become adult stem cells analogous to the mammalian intestinal ones, serves as a unique model for studying how the adult stem cells are formed. To clarify its molecular mechanisms, we here investigated roles of non-canonical Wnt signaling in the larval-to-adult intestinal remodeling during Xenopus laevis metamorphosis.
  
  
  RESULTS
  Our quantitative RT-PCR (qRT-PCR) and immunohistochemical analyses indicated that the expressions of Wnt5a and its receptors, frizzled 2 (Fzd2) and receptor tyrosine kinase-like orphan receptor 2 (Ror2) are up-regulated by T3 and are spatiotemporally correlated with adult epithelial development in the X. laevis intestine. Notably, changes in morphology of larval absorptive epithelial cells expressing Ror2 coincide well with formation of the adult stem cells during metamorphosis. In addition, by using organ cultures of the tadpole intestine, we have experimentally shown that addition of exogenous Wnt5a protein to the culture medium causes morphological changes in the larval epithelium expressing Ror2 even in the absence of T3. In contrast, in the presence of T3 where the adult stem cells are formed in vitro, inhibition of endogenous Wnt5a by an anti-Wnt5a antibody suppressed the epithelial morphological changes, leading to the failure of stem cell formation.
  
  
  CONCLUSIONS
  Our findings strongly suggest that the adult stem cells originate from the larval absorptive cells expressing Ror2, which require Wnt5a/Ror2 signaling for their dedifferentiation accompanied by changes in cell morphology.
authors.affiliation: Department of Biology, Nippon Medical School, Kyonan-cho, Musashino, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ishizuya-Oka
authors.affiliation: Institute of Development and Aging Sciences, Nippon Medical School, Kosugi-cho, Kawasaki, Kanagawa, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Kajita
authors.affiliation: Department of Biology, Nippon Medical School, Kyonan-cho, Musashino, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hasebe
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D054337:Cell Dedifferentiation; D004847:Epithelial Cells / Q000502:physiology*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007422:Intestines / Q000166:cytology; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008675:Metamorphosis, Biological; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014284:Triiodothyronine / Q000502:physiology*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C085096:Wnt5a protein, Xenopus; D029867:Xenopus Proteins; D014284:Triiodothyronine; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C000598273:Ror2 protein, Xenopus