Dynamics of growth and reproduction in fish

• Project/Area Number: 16380128
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General fisheries
• Research Institution: The University of Tokyo
• Principal Investigator: AIDA Katsumi The University of Tokyo, Graduate School of Agricultural and Life Science, Professor, 大学院・農学生命科学研究科, 教授 (50012034)
• Co-Investigator(Kenkyū-buntansha): KANEKO Toyoji The University of Tokyo, Graduate School of Agricultural and Life Science, Associate Professor, 大学院・農学生命科学研究科, 助教授 (70221190)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥15,700,000 (Direct Cost: ¥15,700,000); Fiscal Year 2005: ¥7,600,000 (Direct Cost: ¥7,600,000); Fiscal Year 2004: ¥8,100,000 (Direct Cost: ¥8,100,000)
• Keywords: zebrafish / hypoxia / IGF / IGFBP-1 / development / growth / knock down / アンチセンスモルフォリノ / 性成熟 / 卵黄蓄積 / ティラピア / SSH法 / 肝臓 / fatty acid binding protein / quinone reductase / B-cell translocation gene 4

Research Abstract

Although reduced fetal growth in response to hypoxia has been appreciated for decades, we have a poor understanding of the effects of hypoxia on embryonic development and the underlying cellular and molecular mechanisms. Here we show that hypoxia treatment not only resulted in embryonic growth retardation but also caused significant delay in developmental speed and the timing of morphogenesis in vital organs of zebrafish. Hypoxia strongly induced the expression of insulin-like growth factor (IGF)- binding protein (IGFBP)-1, a secreted protein that binds IGFs in extracellular environments. Hypoxia did not change the expression levels of IGFs, IGF receptors, or other IGFBPs. The hypothesis that elevated IGFBP-1 mediates hypoxia-induced embryonic growth retardation and developmental delay by binding to and inhibiting the activities of IGFs was tested by loss- and gain-of-function approaches. Knockdown of IGFBP-1 significantly alleviated the hypoxia-induced growth retardation and developmental delay. Overexpression of IGFBP-1 caused growth and developmental retardation under normoxia. Furthermore, reintroduction of IGFBP-1 to the IGFBP-1 knocked-down embryos restored the hypoxic effects on embryonic growth and development. When tested in vitro with cultured zebrafish embryonic cells, IGFBP-1 itself had no mitogenic activity, but it inhibited IGF-1- and IGF-2-stimulated cell proliferation. This inhibitory effect was abolished when IGF-1 or IGF-2 was added in molar excess, suggesting that IGFBP-1 inhibits embryonic growth and development by binding to and inhibiting the activities of IGFs. The induction of IGFBP-1 expression may be a conserved physiological mechanism to restrict the IGF-stimulated growth and developmental process under hypoxic stress.

Research Products

• [Journal Article] Understanding hypoxia-induced gene expression in early development : In vitro and in vivo analysis of hypoxia-induced factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression (2006)
  • Author(s): Kajimura, S., Aida, K., Duan, C.
  • Journal Title: Mol. Cell. Biol. 26 Pages: 1142-1155
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Understanding hypoxia-induced gene expression in early development : In vitro and in vivo analysis of hypoxia-induced factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression (2006)
  • Author(s): Kajimura, S., Aida, K., Duan, C.
  • Journal Title: Mol.Cell.Biol. 26 Pages: 1142-1155
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Understanding hypoxia-induced gene expression in early development: In vitro and in vivo analysis of hypoxia-induced factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression (2006)
  • Author(s): Kajimura, S., Aida, K., Duan, C.
  • Journal Title: Mol.Cell.Biol. 26 Pages: 1142-1155
• [Journal Article] Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation (2005)
  • Author(s): Kajimura, S., Aida, K., Duan, C.
  • Journal Title: PNAS 102 Pages: 1240-1245
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Insulin-like growth factor factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation (2005)
  • Author(s): Kajimura, S., Aida, K., Duan, C.
  • Journal Title: PNAS 102 Pages: 1240-1245
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Insulin-like growth factor factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation (2005)
  • Author(s): Kajimura, S., Aida, K., Duan, C
  • Journal Title: PNAS 102 Pages: 1240-1245
• [Journal Article] Changes in brain GnRH mRNA and Pituitary GnRH peptide during testicular maturation in barfin flounder (2004)
  • Author(s): Amano, M., Okubo, K., Yamanome, T., Yamada, H., Aida, K., Yamamori, K.
  • Journal Title: Comp.Biochem.Physiol.part B 183 Pages: 435-443
• [Journal Article] Ontogenic development of three GnRH systems in the brain of pleuronectiform fish, Bartin Flounder (2004)
  • Author(s): Amano, M., Okubo, K., Yamanome, T., Oka, Y., Kawaguchi, N., Yamamori, K., Aida, K.
  • Journal Title: Zool.Soc. 21 Pages: 311-317
• [Journal Article] Identification of the growth hormone receptor in an advanced teleost, the tilapia (Oreochromis mossambicus) with special reference to its distinct expression pattern in the ovary (2004)
  • Author(s): Kajimura, S., Kawaguchi, N., Kaneko, T., Hirano, T., Grau, E.G., Aida, K.
  • Journal Title: J.Endocrinol. 181 Pages: 65-76