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  2. Nutritional control of thyroid morphogenesis through gastrointestinal hormones

Nutritional control of thyroid morphogenesis through gastrointestinal hormones

  • Curr Biol. 2022 Apr 11;32(7):1485-1496.e4. doi: 10.1016/j.cub.2022.01.075.
Maki Takagishi 1 Binta Maria Aleogho 2 Masako Okumura 2 Kaori Ushida 3 Yuichiro Yamada 4 Yusuke Seino 5 Sayoko Fujimura 6 Kaoru Nakashima 6 Asako Shindo 7
Affiliations

Affiliations

  • 1 Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
  • 2 Division of Biological Sciences, Department of Molecular Biology, Nagoya University Graduate School of Science, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
  • 3 Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
  • 4 Kansai Electric Power Medical Research Institute, 2-1-7 Fukushima, Fukushima-ku, Osaka 553-0003, Japan.
  • 5 Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
  • 6 Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
  • 7 Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Division of Biological Sciences, Department of Molecular Biology, Nagoya University Graduate School of Science, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan; Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan. Electronic address: shindo@kumamoto-u.ac.jp.
Abstract

Developing Animals absorb nutrients either through the placenta or from ingested food; however, the mechanisms by which embryos use external nutrients for individual organ morphogenesis remain to be elucidated. In this study, we assessed nutrient-dependent thyroid follicle morphogenesis in Xenopus laevis and investigated the role of secreted gastrointestinal (GI) Hormones post-feeding. We found that feeding triggers thyroid follicle formation, and the thyroid cells showed transient inactivation of cell proliferation after feeding. In addition, the thyroid cells with multi-lumina were frequently observed in the fed tadpoles. The expression of the particular GI hormone incretin, glucose-dependent insulinotropic polypeptide (GIP), responded to feeding in the intestines of Xenopus tadpoles. Inhibition of Dipeptidyl Peptidase 4 (Dpp4), a degradative Enzyme of incretin, increased the size of the thyroid follicles by facilitating follicular lumina connection, whereas inhibition of the sodium-glucose cotransporter (SGLT) reversed the effects of Dpp4 inhibition. Furthermore, injection of GIP peptide in unfed tadpoles initiated thyroid follicle formation-without requiring feeding-and injection of an incretin receptor antagonist suppressed follicle enlargement in the fed tadpoles. Lastly, GIP receptor knockout in neonatal mice showed smaller follicles in the thyroid, suggesting that the GI hormone-dependent thyroid morphogenesis is conserved in mammals. In conclusion, our study links external nutrients to thyroid morphogenesis and provides new insights into the function of GI hormone as a regulator of organ morphology in developing Animals.

Keywords

Xenopus laevis; developmental stasis; gastrointestinal hormone; glucose-dependent insulinotropic polypeptide; incretin; nutrients; thyroid follicle formation; thyroid morphogenesis.

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