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The regulation of cell differentiation and morphogenesis on mamalian early development

Research Project

Project/Area Number 08408033
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionOsaka University

Principal Investigator

HAMADA Hiroshi  Institute for Molecular and Cellular Biology, Osaka University, 細胞生体工学センター, 教授 (00208589)

Co-Investigator(Kenkyū-buntansha) SAIJHO Yukio  Institute for Molecular and Cellular Biology, Osaka University, 細胞生体工学センター, 助手 (20260333)
FUJII Hideta  Institute for Molecular and Cellular Biology, Osaka University, 細胞生体工学センター, 助手 (10273723)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥29,200,000 (Direct Cost: ¥29,200,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥23,300,000 (Direct Cost: ¥23,300,000)
KeywordsLeft-right asymmetry / Lefty / transcriptional regulation
Research Abstract

Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) axis formation. With the use of transgenic analysis, the transcriptional regulatory regions of these genes responsible for their L-R asymmetric expression have now been investigated. The 9.5-kb upstream region of lefty-1 and the 5.5-kb upstream region of lefty-2 reproduced the expression pattern of the corresponding gene. Examination of deletion constructs revealed the presence of a left side-specific enhancer (ASE) that is essential and sufficient for lefty-2 asymmetric expression. In contrast, the asymmetric expression of lefty-1 was shown to be determined by a combination of bilateral enhancers and a right side-specific silencer (RSS). The 9.5-kb region of lefty-1 and the 5.5-kb region of lefty-2 responded to iv and inv, upstream genes of lefty-1 and lefty-2. The regulation of lefty-2 by iv and inv was mediated by ASE. These results suggest that, in spite of the similarities between lefty-1 and lefty-2, different regulatory mechanisms underlie their asymmetric expression.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Mitsuya K.: "Epigenetic reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprinting"Genes Cells. 3. 245-255 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Meno C.: "Lefty-1 is required for letf-right determination as a regulator of lefty-2 and nodal"Cell. 94. 287-297 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshioka H.: "Ptx2, a bicoid homeobox gene, is involved in a Lefty-signaling pathway in determination of left-right asymmetry"Cell. 94. 299-305 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higano-Yamagaishi,K: "Transcriptional regulatory region of Brn-2 required for the expression in olfactory epithelial cells"Dev. Brain Res.. 109. 77-89 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mochizuki T,: "Cloning of inv, a gene that conrols left/right asymmetry and kidney development"Nature. 395. 177-181 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mitsuya, K., Meguro, M., Sui, H., Schulz, T.C., Kugoh, H., Hamada H., and Oshimura, M: "Epigeneric reprogramming of the human H19 gene in mouse embryonic cells does not erase the primary parental imprinting"Genes Cells. 3. 245-255 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Meno, C., Shimono, A., Saijoh, Y., Yashiro, K., Mochida, K., Ohishi, S., Noji, S., Kondoh, H. and Hamada, H: "lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal"Cell. 94. 287-297 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshioka, H., Meno C., Koshiba, K., Sugihara, M., Itoh, H., Ishimaru, Y., Inoue, T., Ohuchi, H., Semina, E.V., Murray, J.C., Hamada, H., and Noji, S.: "Ptx2, a bicoid homeobox gene, is involved in a Lefty-signaling pathway in determination of left-right asymmetry"Cell. 94. 299-305 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hagino-Yamagishi, K., Saijoh, Y., Yamazaki, Y., Yazaki, K., and Hamada, H.: "Transcriptional regulaory region of Brn-2 required for the expression in olfactory epithelial cells"Dev. Brain Res.. 109. 77-89 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mochizuki, T., Saijoh, Y.,Tsuchiya, K., Shirayoshi, Y., Takai. S., Taya, C., Yonekawa, H., Yamada, K., Nihei, H., Nakatsuji, N., Overbeek, P., Hamada,_H., and Yokoyama, T.: "Cloning of inv, a gene that controls left/right asymmetry and kidney development"Nature. 395. 177-181 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saijoh,Y.,: "Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2." Genes & Dev.13. 259-269 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Meno,C.,: "lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal." Cell. 94. 287-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshioka,H.,: "Pts2,a bicoid homeobox gene,is involved in a Lefty-signaling pathway in determination of left-right asymmetry." Cell. 94. 299-305 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujii,H.,: "Metabolic inactivation of retinoic acid by a novel P450 differentially expressed in developing mouse embryos." EMBO J.16. 4163-4173 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Meno,C.,: "Left-right asymmetric expression of unique TGF β-related gene lefty in mouse embryo" Nature. 381. 151-155 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Saijho,Y.,: "Identification of putative downstream genes of Oct-3,a pluripotent cell-specific transcription factor." Genes to Cells. 1. 239-252 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimazaki,T.: "Hybrid cell extinction and re-expression of Oct-3 gene correlates with differentiation potential" EMBO J.12. 4489-4498 (1993)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,H.: "A CNS-specific POU transcription factor,Brn-2,is required for establishing mammalian neural cell lineage" Neuron. 11. 1197-1206 (1993)

    • Related Report
      1997 Annual Research Report
  • [Publications] Saijoh,Y.: "Identification of putative downstream genes of Oct-3 a pluripotent cell-specific transcription factor." Genes to Cells. 1. 239-252 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Meno,C.: "Lefr-right asymmetric expression of the TGf-family member lefty in mouse embryos" Nature. 381. 151-155 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii,H.: "Metabolic inactivation of retinoic acid by a novel P450 differentially expressed in developing mouse embryos" EMBO J.16. 4163-4173 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Meno,C.: "Two closely-related left-right asymmetrically-expressed genes, lefty-1 and lefty-2:Their distinct expression domains,chromosomal linkage and directneuralizing activity in Xenopus embryos." Genes to Cells. 2. 513-524 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Saihoh,Y.,: "Identification of putative downstream genes of Oct-3,a pluripotent cell-specific transcription factor" Genes to Cells. 1. 239-252 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okazawa,H.,: "Bcl-2 inhibits retionoic acid-induced apotosis during the neural differentiation of embryonal stem cells" J.Cell Biol.132. 955-968 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Meno C.,: "Left-right asymmetric expression of the TGF-family member lefty in mouse embryo" Nature. 381. 151-155 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirose,K.,: "cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor(Arnt2)with close sequencesimilarity to the aryl hydrocarbon receptor nuclear translocator(Arnt)" Mol,Cell.Biol.16. 1706-1713 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okazawa,H.,: "Regulation of strial D1A dopamine receptor gene transcription by Brn-4." Proc.Natl.Acad.Aci.USA.93. 11933-11938 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Yamagishi,Y.: "Predominant expression of Brn-2 transcription factor in postmitotic neurons of developing mouse cortex" Brain Res.in press. (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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