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Expression of hyaluronan synthases upregulated by thyroid hormone is involved in intestinal stem cell development during Xenopus laevis metamorphosis

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Abstract

During amphibian intestinal remodeling, thyroid hormone (TH) induces adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian one. We have previously shown that hyaluronan (HA) is newly synthesized and plays an essential role in the development of the stem cells via its major receptor CD44 in the Xenopus laevis intestine. We here focused on HA synthase (HAS) and examined how the expression of HAS family genes is regulated during natural and TH-induced metamorphosis. Our quantitative RT-PCR analysis indicated that the mRNA expression of HAS2 and HAS3, but not that of HAS1 and HAS-rs, a unique Xenopus HAS-related sequence, is upregulated concomitantly with the development of adult epithelial primordia consisting of the stem/progenitor cells during the metamorphic climax. In addition, our in situ hybridization analysis indicated that the HAS3 mRNA is specifically expressed in the adult epithelial primordia, whereas HAS2 mRNA is expressed in both the adult epithelial primordia and nearby connective tissue cells during this period. Furthermore, by treating X. laevis tadpoles with 4-methylumbelliferone, a HA synthesis inhibitor, we have experimentally shown that inhibition of HA synthesis leads to suppression of TH-upregulated expression of leucine-rich repeat-containing G protein-coupled 5 (LGR5), an intestinal stem cell marker, CD44, HAS2, HAS3, and gelatinase A in vivo. These findings suggest that HA newly synthesized by HAS2 and/or HAS3 is required for intestinal stem cell development through a positive feedback loop and is involved in the formation of the stem cell niche during metamorphosis.

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Acknowledgements

This study was supported in part by JSPS KAKENHI Grant Numbers JP17K07475 (T.H.) and JP18K06320 (A. I.-O.).

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Authors and Affiliations

  1. Department of Biology, Nippon Medical School, 1-7-1 Kyonan-cho, Musashino, Tokyo, 180-0023, Japan

    Kenta Fujimoto, Takashi Hasebe & Atsuko Ishizuya-Oka

  2. Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan

    Mitsuko Kajita

Authors
  1. Kenta Fujimoto
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  2. Takashi Hasebe
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  3. Mitsuko Kajita
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  4. Atsuko Ishizuya-Oka
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Correspondence to Atsuko Ishizuya-Oka.

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Communicated by Matthias Hammerschmidt

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Fujimoto, K., Hasebe, T., Kajita, M. et al. Expression of hyaluronan synthases upregulated by thyroid hormone is involved in intestinal stem cell development during Xenopus laevis metamorphosis. Dev Genes Evol 228, 267–273 (2018). https://doi.org/10.1007/s00427-018-0623-x

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