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1996 Fiscal Year Final Research Report Summary

Role of typeIII receptor tyrosine kinases in lympho-hematopoietic tissues

Research Project

Project/Area Number 07457085
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NISHIKAWA Shin-Ichi  Kyoto University Medicine Professor, 医学研究科, 教授 (60127115)

Project Period (FY) 1995 – 1996
KeywordsFlk1 / ES cell / proximal lateral mesoderm / E-cadherin / IL-7 receptor / payr's patch / PDGF reoeptor
Research Abstract

This grant covered three projects to understand the molecular mechanisms underlying development of lymphohematopoietic tissues in the embryo. Followings are the summary of our progress.
1) We attempted to define all intermediate stages in the differentiation pathway towards hematopoietic and vascular endothelial cells. For this purpose, we developed mAbs recognizing PDGFRalpha, c-Kit and Flkl that are expressed distinct subsets of nascent mesoderm of mouse embryo. These surface markers in combination with E-cadherin, V-cadherin, CD34, CD31 and CD45 were successfully used to define probably all possible intermediate stages. We are currently investigating the molecular mechanisms regulating each branching point in this differentiation pathway.
2) Cellular and molecular basis for peyer's patch formation was investigated. While molecular requirements for peyer's patch formation has been elucidated through the analysis of various KO mice, it has been unclear how these molecules like lymphotoxins are involved in the formation of peyer's patch analage. Using IL-7Ralpha-KO mice and an antagonistic anti-IL-7Ralpha-mAb, we found that IL-7Ralpha^+ immature lymphocytes are the inducer of the peyer's patch anlage. This study demonstrated for the first time that immature lymphocyte has its own unique function. Based on this finding, we succeeded to produce mice that lacks peyer's patch but otherwise normal. This model mice will be helpful to understand the role of peyer's patch in the mucosal immunity.
3) In an attempt to understand the development of hematopoietic microenvironment, we found that PDGFRalpha is expressed in the stromal cell component of the fetal liver on which hematopoietic cells are associated. Using Ph/Ph mutant mice that lacks this molecule, we found that adult-type erythropoesis was not initiated in the absence of PDGFRalpha.

  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Torihashi, et al.: "C-kit-dependent development of interstitial cells activity in the murine qastrointestinal tract" Cell and Tissue Res.280. 97-111 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Era t, at al.: "Identification of two transcripts of AML1/ETO. MTG8-fused gene in t (8 ; 21) leukemic cells and expression of wide-type ETO (MTG8) gene in hematopoietic cells" Gen. Chrom. Cancer. 13. 25-33 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunaga M, et al.: "Making in vitro model of B lymphopoiesis real" Seminar Immunol.7. 185-196 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunaga M, et al.: "Cell Cycle Control of c-kit^+IL-7R^+B Precursor Cells by Two Distinct Signals Derived From IL-7-Receptor and c-kit in a Fully Defined Medium." J. Exp. Med.182. 315-323 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Reid K, et al.: "Steel factor requlates melanocyte development through selective survival and proliferation of c-kit^+ progenitors…newborn mice." J. Inv. Dermatol. 105. 322-328 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi SI, et al.: "Identification of the control regions for mouse c-kit gene transcription induced by retinoic acid." DNA research. 2. 211-218 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onodera M, et al.: "Overexpression of retinoic acid receptor a suppresses myeloid cell differentiation at promyelocyte stage" Oncogene. 11. 1291-1298 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sudo T, et al.: "Hieralchical relation of c-kit and c-fms intramarrow production of CEU-M" Oncogene. 11. 2469-2476 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Era T, et al.: "Expression of AML1 and ETO transcripts in hematopoietic cells" Leukemia (supplement). 9. s26-s28 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] TokutomiN, et al.: "Rythmic CI^- current and physiological roles of the intestinal c-kit positive cells" Eur. J. Physiol.431. 169-177 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunaga M, et al.: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor" J. Cell Biol.132. 19-26 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kunisada T, et al.: "Characteization and isolation of melanocyte progenitors from mouse embryos" Dev. Grouth. Diff.38. 87-98 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanatsu M, et al.: "In vitro analysis of epiblast tissue potency for hematopoietic cell differentiation" Development. 122. 831-838 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida H, et al.: "Distinct stage of Melanocyte differentiation revealed by analysis of nonuniform pigmentation patterns" Development. 122. 1207-1214 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh N, et al.: "Role of IL-7 and KL in activation molecules controlling the G1/S transition of B precursor cells" Int. Immunol.8. 317-324 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagasawa T, et al.: "Defects of B lymphopoiesis and bone marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1" Nature. 382. 635-638 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuchida K, et al.: "Molecular cloning of a novel typeI receptor serine/threonine kinase for the TGFb superfamily from rat brain" Mol. Cell. Neurosci.7. 467-478 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takakura N, et al.: "Involvement of platelet derived growth factor receptora in hair canal formation" J. Inv. Dermatol. 107. 770-777 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takakura N, et al.: "PDGFRa expression during mouse embryogenesis : Immunolocalization analyzed by whole mount immunostaining using the monoclonal anti-mouse-PDGFRa antibody APA5." J. Histchem. Cytochem.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takakura N, et al.: "A combination of M-CSF (-) stromal cell line stem cell factor, epidermal growth factor and a chemically defined medium supports preferential proliferation of CFU-c." J. Exp. et al.184. 2301-2311 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida H, et al.: "Neural and skin cell-specific expression pattern conferred by steel factor regulatory sequence in transgenic mice" Dev. Dynamics. 207. 222-232 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Torihashi et al.: "Enteric neurons express steel factor-lacZ transgene in the murine gastrointestinal tract" Brain Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi SI, et al.: "Osteoclast precursors in bone marrow and peritoneal cavity" J. Cell. Physiol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Adachi S, et al.: "Three desitinctive steps in Peyer's patch formation of murine embryo" Int. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida H, et al.: "Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development" Dev. Biol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Torihashi S,Ward SM,Nishikawa Sl, Nishi K,Kobayashi S,Sanders KM: "Kit-dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract." Cell and Tissue Res.280. 97-111 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Era T,Asou N.Kunisada T,Yamasaki H,Asou N,Kamada N.Nishikawa Sl, Yamaguchi K,and Takasuki K: "Identification of two transcripts of AMLI/ETO.MTG8-fused gene in t (8 ; 21) leukemic cells and expression of wild-type ETO (MTG8) gene in hematopoietic cells." Gen.Chrom.Cancer. 13. 25-33 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunaga Y,Itoh T,Adachi S,and Nishikawa SI: "Making in vitro model of B lymphopoiesis real." Seminal Immunol. 7. 185-196 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunaga Y,Wang F-H,Kunisada T,Nishikawa S,and Nishikawa SI: "Cell Cycle Control of c-kit^+ IL-7R^+ B Precurson Cells by Two Distinct Signals Derived From IL-7-Receptor and c-kit in a Fully Defined Medium." J.Exp.Med.182. 315-323 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onodera M,Kunisada T,Nishikawa S,Sakiyama Y,Matsumoto S and Nishikawa SI: "Overexpression of retinoic acid receptor a suppresses myeloid cell differentiation at promyelocyte stage." Oncogene. 11. 1291-1298 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Reid K,Nishikawa SI,Bartlett PF,Murphy M.: "Steel factor regulates melanocyte development through selective survival and proliferation of c-kit^+ progenitors. (44) Okura M,Maeda H,Nishikawa SI,Mizoguchi M.Effects of monoclonal anti-c-kit antibody (ACK2) on melanocyte in newborn mice" J.Inv.Dermatol.105. 322-328 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi SI,Kunisada T,Ogawa M,and Nishikawa S: "Identification of the control regions for mouse c-kit gene transcription induced by retinoic acid." DNA research. 2. 211-218 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sudo T,Nishikawa S,Ogawa M,Kataoka H,Ohno N,Izawa A,Hayashi SI,and Nishikawa SI: "Hieralchical relation of c-kit and c-fms in intramarrow production of CFU-M." Oncogene. 11. 2469-2476 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Era T,Asou N,Yamaguchi K,Yamasaki H,Kamada N,Nishikawa SI and Takatsuki K: "Expression of AMLI and ETO transcripts in hematopoietic cells" Leukemia (supplement). 9. s26-s28 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokutomi N,Maeda, H,Tokutomi Y,Sato D,Sugita M,Nishikawa S,Nishikawa SI,Nakao J,Imamura T,and Nishi K: "Rythmic Cl^- current and physiological roles of the intetstinal c-Kit positive cells" Eur.J.Physiol.431. 169-177 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunaga M,Yagi T,Hanzawa N,Yasuda M,Yamanashi Y,Yamamoto T,Aizawa S,Miyauchi Y,Nishikawa SI: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor" J.Cell Biol.132. 19-26 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kunisada T,Yoshida H,Ogawa M,Shulz LD.and Nishikawa SI: "Characterization and isolation of melanocyte progenitors from mouse embryos" Dev.Growth.Diff.38. 87-98 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanatsu M and Nishikawa SI: "In vitro analysis of epiblast tissue potency for hematopoietic cell differentiation." Development. 122. 831-838 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida H,Kunisaada T,Kusakabe M,Nishikawa S,and Nishikawa SI: "Distinct stages of melanocyte diffemtiation revealed by analysis of nonuniform pigmentation patterns" Development. 122. 1207-1214 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh N,Masahiro Yasunaga M,Hirashima M,Yoshida O,Nishikawa SI: "Role of IL-7 and KL in activating molecules controlling the G1/S transition of B precursor cells" Int.Immunol.8. 317-324 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagasawa T,Hirota S,Tachibana K,Takakura N,Nishikawa SI,Kitamura Y,Yoshida N,Kikutani H,Kishimoto T.: "Defects of B lymphopoiesis and bone marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1." Nature. 382. 635-638 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuchida K,Sawchenko PE,Nishikawa SI,and Vale WW.: "Molecular cloning of a novel typeI receptor serine/threonine kinase for the TGFb superfamily from rat brain." Mol.Cell.Neurosci.7. 467-478 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takakura N,Yoshida H,Kunisada T,and Nishikawa SI: "Involvement of platelet derived growth factor receptora in hair canal formation." J.Inv.Dermatol.107. 770-777 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fruttiger, M., Calver, A., Kruger, W.H., Mudhar, H.S., Michalovich, D., Takakura, N., Nishikawa, S.-i and Richardson, W.D.: "PDGF mediates a neuron-astrocyte interaction in the developing retina." Neuron. 17. 1117-1131 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takakura N,Kodama H,Ogawa M,Nishikawa S,and Nishikawa SI: "Preferential proliferation of murine colony forming units in culture in a chemically defined condition witha macrophage colony stimulating factor negative stromal cell clone" J.Exp.Med.184. 2301-2311 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida H,Hayashi SI,Schulz LD,Yamamura K,Nishikawa S,Nishikawa SI and Kunisada T: "Neural and skin cell-specific expression pattem conferred by steel factor regulatory sequence in transgenic mice" Dev.Dynamics. 207. 222-232 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takakura N,Yoshida H,Ogura Y,Kataoka H,Nishikawa S,and Nishikawa SI: "PDGFRa expression during mouse embryogenesis : Immunolocalization analyzed by whole mount immunostaning using the monoclonal anti-mouse-PDGFRa antibody APA5." J.Histchem.Cytochem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Torihashi S,Yoshida H,Nishikawa SI,and Sanders KM: "Enteric neurons express steel factor-lacZ transgene in the murine gastrointestinal tract." Brain Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi SI,Miyamoto A,Yamane T,Kataoka H,Ogawa M,Sugawara S,Nishikawa S,Nishikawa SI,Sudo T,Yamazaki H,Kunisada T: "Osteoclast precursors in bone marrow and peritoneal cavity." J.Cell.Physiol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Adachi S,Yoshida H,Kataoka H,and Nishikawa SI: "Three distinctive steps in Peyer's patch formation of murine embryo" Int.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida H,Takakura N,Kataoka H,Kunisada T,Okamura H,and Nishikawa SI: "Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development" Dev.Biol. (in press).

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

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Published: 1999-03-09  

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