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1998 Fiscal Year Final Research Report Summary

Characterization of new genes for BMP signaling pathway.

Research Project

Project/Area Number 09680714
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionOkazaki National Research Institutes

Principal Investigator

SHIBUYA Hiroshi  National Institute for Basic Biology, Associate Professor, 基礎生物学研究所, 助教授 (30261324)

Project Period (FY) 1997 – 1998
KeywordsBMP / Dlx5 / osteogenesis / ventralization / TAK1 / Smad / ATF2
Research Abstract

TAK1, a member of the MAP kinase kinase kinase family, and its activator, TAB1, participate in the bone morphogenetic protein (BMP) signaling pathway involved in mesoderm induction and patterning in early Xenopus embryos.However, the events leading from receptor activation to TAK1 activation remain to be identified.A yeast interaction screen was used to search for proteins that function in the pathway linking the receptors and TAB1-TAK1.The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein.XIAP associated not only with TAB1 but also with the BMP receptors in mammalian cells. Injection of XIAP mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos in a TAB1-TAK1-dependent manner.Furthermore, a truncated form of XIAP lacking the TAB1-binding domain partially blocked the expression of ventral mesodermal marker genes induced by a constitutively-active BMP type I receptor.Taken together, we identified that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptors and TAB1-TAK1.
Recently, we isolated a murine homeobox-containing gene, distal-less 5 (mDlx5), as a BMP-inducible gene in osteoblastic MC3T3-E1 cells.Stable transfectants of MC3T3-E1 that overexpress mDlx5 mRNA showed increase in various osteogenic markers ; a 4-fold increase in alkaline phosphatase activity, a 6-fold increase in osteocalcin production and appearance in mineralization of extracellular matrix.Furthermore, mDlx5 was induced orthotopically in mouse embryos treated with BMP-4 and in fractured bone of adult mice. Consistent with these observations, we also found that injection of mDlx5 mRNA in dorsal blastomeres enhanced the ventralization of Xenopus embryos.Our results indicated that mDlx5 is a target gene of the BMP signaling pathway and acts as an important regulator of both osteogenesis and dorso-ventral patterning of embryonic axis.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Shibuya et al.: "Role of TAK1 and TAB1 in BMP signaling in early Xenopus development." EMBO J.17. 1019-1028 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurozumi et al: "BRAM1,a BMP receptor-associated molecule involved in BMP signalling." Genes to Cells. 3. 257-264 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaguchi et al.: "XIAP,a cellular member of the inhibitor of apoptosis protein family,links the receptors to TAB1-TAK1 in the BMP signaling pathway." EMBO J.18. 179-187 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamada et al.: "Nagative regulation of Wingless signaling by D-Axin,a Drosophila homo-logue of Axin." Science. 283. 1739-1742 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyama et al.: "A BMP-inducible gene,Dlx5 regulates osteoblast differentiation and meso-derm induction." Dev.Biol.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masuyama et al.: "Identification of two Smad4s in Xenopus:Their common and distinct proper-ties." J.Biol.Chem.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibuya, H., Iwata, H., Masuyama, N., Gotoh, Y., Yamaguchi, K., Irie, K., Matsumoto, K., Nishida, E.and Ueno, N.: "Role of TAKI and TAB1 in BMP signaling in early Xenopus development." EMBO J.17. 1019-1028 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurozumi, K., Nishita, M., Yamaguchi, K., Fujita, T., Ueno, N.and Shibuya, H.: "BRAM1, a BMP receptor-associated molecule involved in BMP signalling" Genes Cells. 3. 257-264 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamaguchi, K., Nagai, S., Ninomiya-Tsuji, J., Nishita, M., Tamai, K., Irie, K., Ueno, N., Nishida, E., Shibuya, H.and Matsumoto, K.: "XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway." EMBO J.18. 179-187 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamada, F., Tomoyasu, Y., Takatsu, Y., Nakamura, M., Nagai, S., Suzuki, A., Fujita, F., Shibuya, H., Toyoshima, K., Ueno, N.and Akiyama, T: "Nagative regulation of Wingless signaling by D-Axin, a Drosophila homologue of Axin." Science. 283. 1739-1742 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyama, K., Yamada, G., Yamamoto, T., Takagi, C., Miyado, K., Sakai.M., Ueno, N and Shibuya, H.: "A BMP-inducible gene, Dlx5 regulates osteoblast differentiation and mesoderm induction." Dev.Biol. (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masuyama, N., Hanafusa, H., Kusakabe, M., Shibuya, H.and Nishida, E.: "Identification of two Smad4s in Xenopus : Their common and distinct properties." J.Biol.Chem.(in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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