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PLoS One 2014 Jan 01;99:e107611. doi: 10.1371/journal.pone.0107611.
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Thyroid hormone-regulated Wnt5a/Ror2 signaling is essential for dedifferentiation of larval epithelial cells into adult stem cells in the Xenopus laevis intestine.

Ishizuya-Oka A , Kajita M , Hasebe T .

BACKGROUND AND AIMS: 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. METHODS/FINDINGS: 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. SIGNIFICANCE: 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.

PubMed ID: 25211363
PMC ID: PMC4161470
Article link: PLoS One

Species referenced: Xenopus laevis
Genes referenced: fzd2 krt19 msi1 pcna ror2 wnt5a
Antibodies: Fzd2 Ab1 Krt19 Ab1 Msi1 Ab1 Pcna Ab4 Ror2 Ab1 Wnt5a Ab1

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References [+] :
Allgeier, WNT5A selectively inhibits mouse ventral prostate development. 2008, Pubmed