Cell and Tissue Research

, Volume 365, Issue 2, pp 309–318 | Cite as

Thyroid hormone activates Wnt/β-catenin signaling involved in adult epithelial development during intestinal remodeling in Xenopus laevis

  • Takashi Hasebe
  • Kenta Fujimoto
  • Mitsuko Kajita
  • Atsuko Ishizuya-OkaEmail author
Regular Article


During amphibian intestinal remodeling, thyroid hormone (TH) induces some larval epithelial cells to dedifferentiate into adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian epithelium. To clarify molecular mechanisms underlying adult epithelial development, we here focus on TH response genes that are associated with the canonical Wnt pathway. Our quantitative reverse transcription plus polymerase chain reaction and immunohistochemical analyses indicate that all of the genes examined, including β-catenin, c-Myc and secreted frizzle-related protein 2 (SFRP2), are up-regulated in Xenopus laevis intestine during both natural and TH-induced metamorphosis. Moreover, immunoreactivity for nuclear β-catenin becomes detectable in adult stem cells from the start of their appearance and then increases in intensity in adult epithelial primordia derived from the stem cells, which actively proliferate and coexpress Wnt target genes c-Myc and LGR5. These expression profiles strongly suggest the involvement of the canonical Wnt pathway in the maintenance and/or proliferation of adult stem/progenitor cells. More importantly, by using organ cultures of the tadpole intestine, we have experimentally shown that the addition of exogenous SFRP2 protein to the culture medium promotes cell proliferation of the adult epithelial primordia, whereas inhibition of endogenous SFRP2 by its antibody suppresses their proliferation. The inhibition of SFRP2 suppresses larval epithelial changes in shape from simple columnar to stem-cell-like roundish cells, resulting in the failure of epithelial dedifferentiation. Thus, TH-up-regulated SFRP2 in the postembryonic intestine promotes adult stem cell development, possibly by acting as an agonist of both canonical and non-canonical Wnt signaling.


Wnt/β-catenin signaling Secreted frizzle-related protein 2 (SFRP2) Intestinal remodeling Adult stem cell Xenopus laevis 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Takashi Hasebe
    • 1
  • Kenta Fujimoto
    • 1
  • Mitsuko Kajita
    • 2
  • Atsuko Ishizuya-Oka
    • 1
    Email author
  1. 1.Department of BiologyNippon Medical SchoolMusashinoJapan
  2. 2.Department of Molecular BiologyInstitute for Advanced Medical Sciences, Nippon Medical SchoolKawasakiJapan

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