腎・尿管の器官・組織形成異常の形成機構に基づく治療・予防法の開発

• Project/Area Number: 19659414
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Shimane University
• Principal Investigator: 大谷 浩 Shimane University, 医学部, 教授 (20160533)
• Co-Investigator(Kenkyū-buntansha): 松本 暁洋 島根大学, 医学部, 助教 (70346378)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2009: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2008: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 尿管 / 腎臓 / ネフロン / 子宮外発生法 / マウス胚 / Wnt5a / 収斂伸長 / FGF7

Research Abstract

1) 腎の位置・形態異常に関する研究
DNA合成期に核に取り込まれるbromo-deoxyuridineにより細胞を標識して追跡し、尿管上皮細胞の移動について詳細に解析した。その解析結果から、尿管の伸長には、胎生11日ごろには収斂伸長(convergent extension)のメカニズムが関わること、しかしそれのみならず、特に胎生12日以降には、部位特異的な細胞増殖の差も伸長に関わることが明らかになった。また尿管の伸長に偏りのある左右差があることが観察された。カエル初期胚の脊索伸長などにおける形態形成の調節因子であるWnt5aを、引き続き、子宮外発生法によりマウス胎児尿管の周囲に注入し、腎臓の位置・形態変化における効果を検証した。腎が骨盤位にある胎生11日に、一側の腎周囲結合組織に分子を注入し、腎が上昇する12日以降に胎児を得て、上昇度、尿管長、尿管芽の分枝、尿細管形成について解析した。現在まで試みた実験条件では、操作側と対照側の間の差が一定の傾向を認めるものの、個体差以上に有意であることが確認できなかった。複数分子との同時注入など、さらなる条件の検討が必要である。
2) ネフロン数の変異に関する研究
ネフロン数の計測法について、さらに検討を進めた。また、培養実験の報告に基づいて投与量および投与時期などの条件を変えながら、引き続き順次注入実験を進めているが、今のところネフロン数の増減について明確な結論を得るに至っておらず、さらに詳細な条件の検討が必要である。

Research Products

• [Journal Article] Ror2 is required for midgut elongation during mouse development (2010)
  • Author(s): Makiko Yamada
  • Journal Title: Developmental Dynamics 239 Pages: 941-953
  • Peer Reviewed
• [Journal Article] Maternal leukemia inhibitory factor (LIF) promotes fetal neurogenesisvia a LIF-ACTH-LIF signaling relay pathway (2010)
  • Author(s): Eriko Simamura
  • Journal Title: Endocrinology 151(in press)
  • Peer Reviewed
• [Journal Article] Multidimensional standard curve for the development processof human fetuses (2010)
  • Author(s): N.Naito
  • Journal Title: Statistics in Medicine (in press)
  • Peer Reviewed
• [Journal Article] Development of olfactory epithelium in the human fetus : scanningelectron microscopic observations (2009)
  • Author(s): Mitsuhiro Kimura
  • Journal Title: Congenit Anom 49 Pages: 102-107
  • Peer Reviewed
• [Journal Article] Role of interleukin-15 in development of the mouse olfactory nerve (2009)
  • Author(s): Tsuyoshi Umehara
  • Journal Title: Congenit Anom 49 Pages: 253-257
  • Peer Reviewed
• [Journal Article] Development of olfactory epithelium in the human fetus : scanning electron microscopic observations (2009)
  • Author(s): Mitsuhiro Kimura
  • Journal Title: Congenit Anom (Kyoto) 49(in press)
  • Peer Reviewed
• [Journal Article] Adrenocortropic hormone affects nonapoptotic cell death of undiffer entiated germ cells in fetal mouse testis. : In vivo study by exo utero transplantation of corticotropic tumor cells into embryos (2008)
  • Author(s): Masayuki Nimura
  • Journal Title: Congenit Anom (Kyoto) 48 Pages: 81-86
  • Peer Reviewed
• [Journal Article] Partial functional overlap of the three ras genes in mouseembryonicdevelopment (2008)
  • Author(s): K Nakamura
  • Journal Title: Oncogene 27 Pages: 2961-2968
  • Peer Reviewed
• [Journal Article] Mouse exo utero development system : protocol and trouble shooting (2008)
  • Author(s): Makiko Yamada
  • Journal Title: Congenit Anom (Kyoto) 48 Pages: 183-187
  • Peer Reviewed
• [Journal Article] Effects of phytoncides on spontaneous activities and sympathetic stress responses in Wistar Kyoto and Stroke-Prone Spontaneously Hypertensive Rats (2008)
  • Author(s): Mai Kawamoto
  • Journal Title: Shimane J. Medical Science 25 Pages: 7-12
  • Peer Reviewed
• [Journal Article] 生活習慣病の素因としての全身臓器の組織形成の解析-臓器の組織形成と疾病素因- (2008)
  • Author(s): 大谷 浩
  • Journal Title: 島根医学 28 Pages: 266-279
  • Peer Reviewed
• [Journal Article] Morphometric study on the characteristic external features of normal and abnormal human embryos (2008)
  • Author(s): Hiroki Otani
  • Journal Title: Congenital Anomalies 48 Pages: 18-28
  • Peer Reviewed
• [Journal Article] Adrenocorticotropic hormone affects nonapoptotic cell death of undifferentiated germ cells in fetal mouse testis.: In vivo study by exo utero transplantation of corticotropic tumor cells into embryos (2008)
  • Author(s): Masayuki Nimura
  • Journal Title: Congenital Anomalies 48 Pages: 81-86
  • Peer Reviewed
• [Journal Article] Fetal jaw movement affects development of articular disk in the temporomandibular joint (2007)
  • Author(s): Hasina Habib
  • Journal Title: Congenital Anomalies 47 Pages: 53-57
  • Peer Reviewed
• [Journal Article] Development of the Pons in Human Fetuses (2007)
  • Author(s): Toshihisa Hatta
  • Journal Title: Congenital Anomalies 47 Pages: 63-67
  • Peer Reviewed
• [Journal Article] Roles of leptin in prenatal and perinatal brain development (2007)
  • Author(s): Jun Udagawa
  • Journal Title: Congenital Anomalies 47 Pages: 77-83
  • Peer Reviewed
• [Journal Article] Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo (2007)
  • Author(s): Sinya Oki
  • Journal Title: Development 134 Pages: 3893-3904
  • Peer Reviewed
• [Journal Article] Partial functional overlap of the three ras genes in mouse embryonic development
  • Author(s): Kenji Nakamura
  • Journal Title: Oncogene (in press)
  • Peer Reviewed
• [Presentation] Relationship between neurotrophin 3 and neuropeptide Y in myelination of the mouse cerebrum during the lactation period (2010)
  • Author(s): Ryuju Hashimoto
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-30
• [Presentation] Adrenocorticotropic tumor cells transplanted into mouse embryos affected pancreatic histogenesis (2010)
  • Author(s): Mai Kawamoto
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-30
• [Presentation] Roles of Ror2 in midgut elongation during mouse development (2010)
  • Author(s): 山田真紀子
  • Organizer: 第115回日本解剖学会全国学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-03-29
• [Presentation] Effects of fetal jaw movement restriction on molecular cascade including Indian hedgehog in the development of condylar cartilage of mandible in mice (2010)
  • Author(s): Esrat Jahan
  • Organizer: 第115回日本解剖学会全国学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-03-28
• [Presentation] Mathematical analysis of mandibular morphogenesis during its prenatal and postnatal development (2010)
  • Author(s): Rafiq Ashiq M
  • Organizer: 第115回日本解剖学会全国学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-03-28
• [Presentation] 筋腱結合部の形成過程における微細構造変化と細胞外マトリクスの形態学的解析 (2010)
  • Author(s): 井上隆之
  • Organizer: 第115回日本解剖学会全国学術集会
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-03-28
• [Presentation] Histogenesis of organs as a predisposing factor to postnatal diseases(セミナー) (2009)
  • Author(s): Hiroki Otani
  • Organizer: International Seminar 「DOHaD : Developmental Origins of Health and Disease」
  • Place of Presentation: Izumo, Japan
  • Year and Date: 2009-07-06
• [Presentation] Fetal jaw movement restriction may affect molecular cascade including Indian hedgehoe in the development of condylar cartilage of mandible (2009)
  • Author(s): Esrat Jahan
  • Organizer: 第55回国際外科学会日本部会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-04
• [Presentation] 3-D study of morphogenesis of mandible ; mathematical analysis of its prenatal and postnatal development (2009)
  • Author(s): Ashiq Mahmood Rafiq
  • Organizer: 第55回国際外科学会日本部会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-04
• [Presentation] マウス中枢神経系発生における顆粒球・マクロファージコロニー刺激因子の機能の解析 (2009)
  • Author(s): 松本暁洋
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-06-26
• [Presentation] Ror2 receptor tyrosine kinase is differentially expressed along AP axis of mouse embryonic gut (2009)
  • Author(s): 山田真紀子
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-06-26
• [Presentation] マウス胚への副腎皮質刺激ホルモン産生腫瘍細胞の移植による膵臓の組織形成への影響の解析 (2009)
  • Author(s): 河本舞
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-06-26
• [Presentation] 発生・発達中の体肢の筋腱結合部におけるfibronectinの発現パターン (2009)
  • Author(s): 井上隆之
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-06-26
• [Presentation] 形態形成にかかわる遺伝子カスケード研究の進歩(シンポジウム) (2009)
  • Author(s): 大谷浩
  • Organizer: 第49回日本先天異常学会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2009-06-25
• [Presentation] Histogenesis of organs as a predisposing factor to postnatal diseases(招待講演) (2009)
  • Author(s): Hiroki Otani
  • Organizer: 18th Lake Shirakaba Conference
  • Place of Presentation: Vedbaek, Denmark
  • Year and Date: 2009-06-20
• [Presentation] マウス腸管の形態形成におけるRor2受容体チロシンキナーゼの発現パターンとその役割 (2009)
  • Author(s): 山田真紀子
  • Organizer: 第42回日本発生生物学会
  • Place of Presentation: 新潟市
  • Year and Date: 2009-05-29
• [Presentation] 臓器の組織形成と疾病の素因形成のかかわり. (シンポジウム) (2008)
  • Author(s): 大谷 浩
  • Organizer: 第24回日本糖尿病・妊娠学会
  • Place of Presentation: 高崎市
  • Year and Date: 2008-11-28
• [Presentation] Expression patterns of Ror2 receptor tyrosine kinase in mousegut development (2008)
  • Author(s): Yamada M
  • Organizer: 第41回日本発生生物学会
  • Place of Presentation: 徳島市
  • Year and Date: 2008-05-28
• [Presentation] Leptin affects the development of the cerebral cortex during theprenatal period. (Special Symposium) (2008)
  • Author(s): Jun Udagawa
  • Organizer: 15th Congress of the FAOPS 2008
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2008-05-24
• [Presentation] Different phases of human development: contributing factors and medical significances (2008)
  • Author(s): Hiroki Otani
  • Organizer: International Symposium: Mathematical Analyses of Human Development
  • Place of Presentation: Matsue, Japan
  • Year and Date: 2008-01-18
• [Presentation] Analysis of myelination and differentiation of oligodendrocytes in the cerebrum of obese mice(ob/ob)in the postnatal period (2007)
  • Author(s): J. Udagawa
  • Organizer: 37th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-05
• [Presentation] ヒト胎児発生過程の調和度解析 (2007)
  • Author(s): 内藤貫太
  • Organizer: 2007年度統計関連学会連合大会
  • Place of Presentation: 神戸市
  • Year and Date: 2007-09-09