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Thyroid hormone-induced expression of a bZip-containing transcription factor activates epithelial cell proliferation during Xenopus larval-to-adult intestinal remodeling

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Abstract

In the intestine during amphibian metamorphosis, stem cells appear, actively proliferate, and differentiate into an adult epithelium analogous to the mammalian counterpart. To clarify the molecular mechanisms regulating this process, we focused on a bZip-containing transcription factor (TH/bZip). We previously isolated TH/bZip from the Xenopus intestine as one of the candidate genes involved in adult epithelial development. Northern blot and in situ hybridization analyses showed that the transient and region-dependent expression of TH/bZip mRNA correlates well with the growth of adult epithelial primordia originating from the stem cells throughout the Xenopus intestine. To investigate its role in the adult epithelial development, we established an in vitro gene transfer system by using electroporation and organ culture techniques, and we overexpressed TH/bZip in the epithelium of Xenopus tadpole intestines. In the presence of thyroid hormone (TH) where the adult epithelial primordia appeared after 3 days of cultivation, overexpression of TH/bZip significantly increased their proliferating activity. On the other hand, in the absence of TH where the epithelium remained as larval-type without any metamorphic changes, ectopic expression of TH/bZip significantly increased the proliferating activity of the larval epithelium but had no effects on its differentiated state. These results indicate that TH/bZip functions as a growth activator during amphibian intestinal remodeling, although TH/bZip expression in the epithelium alone is not sufficient for inducing the stem cells.

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References

  • Amano T, Yoshizato K (1998) Isolation of genes involved in intestinal remodeling during anuran metamorphosis. Wound Repair Regen 6:302–313

    Article  PubMed  CAS  Google Scholar 

  • Berry DL, Rose CS, Remo BF, Brown DD (1998a) The expression pattern of thyroid hormone response genes in remodeling tadpole tissue defines distinct growth and resorption gene expression programs. Dev Biol 203:24–35

    Article  CAS  Google Scholar 

  • Berry DL, Schwartzman RA, Brown DD (1998b) The expression pattern of thyroid hormone response genes in the tadpole tail identifies multiple resorption programs. Dev Biol 203:12–29

    Article  CAS  Google Scholar 

  • Booth C, Potten CS (2000) Gut instincts: thoughts on intestinal epithelial stem cells. J Clin Invest 105:1493–1499

    Article  PubMed  CAS  Google Scholar 

  • Brown DD, Wang Z, Furlow JD, Kanamori A, Schwartzman RA, Remo BF, Pinder A (1996) The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis. Proc Natl Acad Sci USA 93:1924–1929

    Article  PubMed  CAS  Google Scholar 

  • Buchholz DR, Hsia S-CV, Fu L, Shi Y-B (2003) A dominant-negative thyroid hormone receptor blocks amphibian metamorphosis by retaining corepressors at target genes. Mol Cell Biol 23:6750–6758

    Article  PubMed  CAS  Google Scholar 

  • Buckbinder L, Brown DD (1992) Thyroid hormone-induced gene expression changes in the developing frog limb. J Biol Chem 267:25786–25791

    PubMed  CAS  Google Scholar 

  • Cowell IG, Hurst HC (1994) Transcriptional repression by the human TH/bZip factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res 22:59–65

    Article  PubMed  CAS  Google Scholar 

  • Cowell IG, Skinner A, Hurst HC (1992) Transcriptional repression by a novel member of the TH/bZip family of transcription factors. Mol Cell Biol 12:3070–3077

    PubMed  CAS  Google Scholar 

  • Damjanovski S, Sachs LM, Shi Y-B (2002) Function of thyroid hormone receptors during amphibian development. Methods Mol Biol 202:153–176

    PubMed  CAS  Google Scholar 

  • Denver RJ, Pavgi S, Shi Y-B (1997) Thyroid hormone-dependent gene expression program for Xenopus neural development. J Biol Chem 272:8179–8188

    Article  PubMed  CAS  Google Scholar 

  • Dodd MHI, Dodd JM (1976) The biology of metamorphosis. In: Lofts B (ed) Physiology of the Amphibia. Academic, New York, pp 467–599

    Google Scholar 

  • Fu L, Buchholtz D, Shi Y-B (2002) Novel double promoter approach for identification of transgenic animals: a tool for in vivo analysis of gene function and development of gene-based therapies. Mol Reprod Dev 62:470–476

    Article  PubMed  CAS  Google Scholar 

  • Furlow JD, Brown DD (1999) In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis. Mol Endocrinol 13:2076–2089

    Article  PubMed  CAS  Google Scholar 

  • Hourdry J, Dauca M (1977) Cytological and cytochemical changes in the intestinal epithelium during anuran metamorphosis. Int Rev Cytol Suppl 5:337–385

    Google Scholar 

  • Ishizuya-Oka A, Shimozawa A (1991) Induction of metamorphosis by thyroid hormone in anuran small intestine cultured organotypically in vitro. In Vitro Cell Dev Biol 27A:853–857

    Article  PubMed  CAS  Google Scholar 

  • Ishizuya-Oka A, Shimozawa A (1992) Connective tissue is involved in adult epithelial development of the small intestine during anuran metamorphosis in vitro. Roux’s Arch Dev Biol 201:322–329

    Article  Google Scholar 

  • Ishizuya-Oka A, Shimozawa A, Takeda H, Shi Y-B (1994) Cell-specific and spatio-temporal expression of intestinal fatty acid-binding protein gene during metamorphosis. Roux’s Arch Dev Biol 204:150–155

    Article  Google Scholar 

  • Ishizuya-Oka A, Ueda S (1996) Apoptosis and cell proliferation in the Xenopus small intestine during metamorphosis. Cell Tissue Res 286:467–476

    Article  PubMed  CAS  Google Scholar 

  • Ishizuya-Oka A, Ueda S, Damjanovski S, Li Q, Liang VC-T, Shi Y-B (1997a) Anteroposterior gradient of epithelial transformation during amphibian intestinal remodeling: immunohistochemical detection of intestinal fatty acid-binding protein. Dev Biol 192:149–161

    Article  CAS  Google Scholar 

  • Ishizuya-Oka A, Ueda S, Shi Y-B (1997b) Temporal and spatial regulation of a putative transcriptional repressor implicates it as playing a role in thyroid hormone-dependent organ transformation. Dev Genet 20:329–337

    Article  CAS  Google Scholar 

  • Ishizuya-Oka A, Inokuchi T, Ueda S (1998) Thyroid hormone-induced apoptosis of larval cells and differentiation of pepsinogen-producing cells in the stomach of Xenopus laevis in vitro. Differentiation 63:59–68

    Article  PubMed  CAS  Google Scholar 

  • Ishizuya-Oka A, Ueda S, Inokuchi T, Amano T, Damjanovski S, Stolow M, Shi Y-B (2001) Thyroid hormone-induced expression of Sonic hedgehog correlates with adult epithelial development during remodeling of the Xenopus stomach and intestine. Differentiation 69:27–37

    Article  PubMed  CAS  Google Scholar 

  • Ishizuya-Oka A, Shimizu S, Sakakibara S, Okano H, Ueda S (2003) Thyroid hormone-up-regulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling. J Cell Sci 116: 3157–3164

    Article  PubMed  CAS  Google Scholar 

  • Kikuyama S, Kawamura K, Tanaka S, Yamamoto K (1993) Aspects of amphibian metamorphosis: hormonal control. Int Rev Cytol 145: 105–148

    PubMed  CAS  Google Scholar 

  • McAvoy JW, Dixon KE (1977) Cell proliferation and renewal in the small intestinal epithelium of metamorphosing adult Xenopus laevis. J Exp Zool 202:129–138

    Article  Google Scholar 

  • McAvoy JW, Dixon KE (1978) Cell specialization in the small intestinal epithelium of adult Xenopus laevis. J Anat 125:155–169

    PubMed  CAS  Google Scholar 

  • Nieuwkoop PD, Faber J (1967) Normal table of Xenopus laevis (Darwin). North-Holland, Amsterdam

    Google Scholar 

  • Potten CS, Booth C, Tudor GL, Booth D, Brady G, Hurley P, Ashton G, Clarke R, Sakakibara S, Okano H (2003) Identification of a putative intestinal stem cell and early lineage marker; Musashi-1. Differentiation 71:28–41

    Article  PubMed  CAS  Google Scholar 

  • Sakamoto N, Fukuda K, Watanuki K, Sakai D, Komano T, Scotting PJ, Yasugi S (2000) Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial–mesenchymal interactions in the developing chicken stomach. Dev Biol 223:103–113

    Article  PubMed  CAS  Google Scholar 

  • Shi Y-B (1999) Amphibian metamorphosis: from morphology to molecular biology. Wiley-Liss, New York

    Google Scholar 

  • Shi Y-B, Brown DD (1993) The earliest changes in gene expression in tadpole intestine induced by thyroid hormone. J Biol Chem 268:20312–20317

    PubMed  CAS  Google Scholar 

  • Shi Y-B, Ishizuya-Oka (1996) Biphasic intestinal development in amphibians: embryogenesis and remodeling during metamorphosis. Curr Top Dev Biol 32:205–235

    Article  PubMed  CAS  Google Scholar 

  • Shi Y-B, Ishizuya-Oka (2001) Thyroid hormone regulation of apoptotic tissue remodeling: implications from molecular analysis of amphibian metamorphosis. Prog Nucleic Acid Res Mol Biol 65:53–100

    PubMed  CAS  Google Scholar 

  • Shimizu K, Ishizuya-Oka A, Amano T, Yoshizato K, Ueda S (2002) Isolation of connective-tissue-specific genes involved in Xenopus intestinal remodeling: thyroid hormone up-regulates Tolloid/BMP-1 expression. Dev Genes Evol 212:357–364

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Brown DD (1993) Thyroid-hormone-induced gene expression program for amphibian tail resorption. J Biol Chem 268:16270–16278

    PubMed  CAS  Google Scholar 

  • Yasugi S, Nakamura H (2000) Gene transfer into chicken embryos as an effective system of analysis in developmental biology. Develop Growth Differ 42:195–197

    Article  CAS  Google Scholar 

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Acknowledgement

We would like to thank Prof. K. Yoshizato for generously supplying the IA009 cDNA fragment and for his encouragement during the course of this work. This work was supported by JSPS Grants-in-Aid for Scientific Research (C) (to A. I.-O.) and the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, (to Y.-B. S.).

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Authors and Affiliations

  1. Life Science Institute, Sophia University, Chiyoda-ku, Tokyo, 102-8554, Japan

    Masayuki Ikuzawa, Shigeki Yasumasu & Ichiro Iuchi

  2. Yoshizato Project, CLUSTER, Hiroshima Prefectural Institute of Industrial Science and Technology, Higashi-Hiroshima, Hiroshima, 739-0046, Japan

    Katsuhiko Shimizu

  3. Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, MD, 20892-5431, USA

    Yun-Bo Shi

  4. Department of Biology, Nippon Medical School, Kawasaki, Kanagawa, 211-0063, Japan

    Atsuko Ishizuya-Oka

Authors
  1. Masayuki Ikuzawa
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  2. Katsuhiko Shimizu
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  3. Shigeki Yasumasu
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  4. Ichiro Iuchi
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  5. Yun-Bo Shi
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  6. Atsuko Ishizuya-Oka
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Correspondence to Atsuko Ishizuya-Oka.

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Communicated by R.P. Elinson

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Ikuzawa, M., Shimizu, K., Yasumasu, S. et al. Thyroid hormone-induced expression of a bZip-containing transcription factor activates epithelial cell proliferation during Xenopus larval-to-adult intestinal remodeling. Dev Genes Evol 216, 109–118 (2006). https://doi.org/10.1007/s00427-005-0037-4

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  • DOI: https://doi.org/10.1007/s00427-005-0037-4

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