Crucial roles of SOX17 in liver-gallbladder-pancreas development

• Project/Area Number: 21248034
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: The University of Tokyo
• Principal Investigator: KANAI Yoshiakira 東京大学, 大学院・農学生命科学研究科, 准教授 (30260326)
• Co-Investigator(Kenkyū-buntansha): TAYA Chouji 公益財団法人東京都医学総合研究所, 基盤技術研究センター, 室長 (90175456) ; KUROHMRU Masamichi 東京大学, 大学院・農学生命科学研究科, 教授 (00148636) ; TSUNEKAWA Naoki 東京大学, 大学院・農学生命科学研究科, 助教 (50431838)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000); Fiscal Year 2011: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2010: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2009: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
• Keywords: SOX17 / 肝臓 / 膵臓 / 胆管 / モデル動物 / マウス / 胆嚢

Research Abstract

The SOX17-positive gallbladder and bile-duct progenitors are specified in the paired lateral endoderm domains outside the heart field at almost the same timing as hepatic and pancreatic induction in early somite stage embryos. These paired Sox17-positive domains expand ventromedially to merge in the midline of the AIP-lip and become localized between the liver and pancreatic primordia. Genetic analyses using Sox17-null and chimeric embryos showed that Sox17 functions cell-autonomously to specify the gallbladder/bile-duct progenitors at the early somite stage. During late-organogenic stages, we also found that insufficient SOX17 expression in the fetal gallbladder and bile-duct epithelia leads to aberrant formation of both gallbladder and cystic duct at the late-fetal stage.

Research Products

• [Journal Article] Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice (2013)
  • Author(s): Uemura. Mami., Ozawa A. Nagala T. Kurosawa K., Tsurukawa. K., Nobuhisa I., Taka T. Mara. K., Kudo, A., Kawakami. H., Saijoh. Y. Kurohmaru M. Kanai, Azuma. M., Kanai. Yoshiakira.
  • Journal Title: Development Volume: 140 Issue: 3 Pages: 639-648
  • DOI: 10.1242/dev.086702
  • Peer Reviewed
• [Journal Article] gonadogenesis in mammals: Significance of long and narrow gonadal struc (2013)
  • Author(s): Harikae K, Miura K, Kanai Y.
  • Journal Title: Developmental Dynamics Volume: (印刷中) Issue: 4 Pages: 2426-2435
  • DOI: 10.1002/dvdy.23872
  • Peer Reviewed
• [Journal Article] Gut endoderm is involved in the transfer of left-right asymmetry from the node to the lateral plate mesoderm in the mouse embryo. (2012)
  • Author(s): Saund RS, Kanai-Azuma M, Kanai Y, Kim I, Lucero MT, Saijoh Y.
  • Journal Title: Development Volume: 139(13) Issue: 13 Pages: 2426-2435
  • DOI: 10.1242/dev.079921
  • Peer Reviewed
• [Journal Article] Dynamics of GFR α 1-positive spermatogonia at the early stages ofcolonization in the recipient testes of W/Wν male mice. (2012)
  • Author(s): 永井遼平
  • Journal Title: Developmental Dynamics Volume: 241 Issue: 8 Pages: 1374-1384
  • DOI: 10.1002/dvdy.23824
  • Peer Reviewed
• [Journal Article] Cbx2, a polycomb group gene, is required for Sry gene expression in mice. (2012)
  • Author(s): Katoh-Fukui Y, Miyabayashi K, Komatsu T, Owaki A, Baba T., Shima, Y, Kidokoro T, Kanai Y, Schedl A, Wilhelm D, Koopman P, Okuno Y, Morohashi K.
  • Journal Title: Endocrinology Volume: 153(2) Issue: 2 Pages: 913-924
  • DOI: 10.1210/en.2011-1055
  • Peer Reviewed
• [Journal Article] Sox17-dependent gene expression and early heart and gut development in Sox17-deficient mouse embryos. (2011)
  • Author(s): Pfister S, Jones VJ, Power M, Truisi GL, Khoo PL, Steiner KA, Kanai-Azuma M, Kanai Y, Tam PP, Loebel DA.
  • Journal Title: Int J Dev Biol. Volume: 55(1) Issue: 1 Pages: 45-58
  • DOI: 10.1387/ijdb.103158sp
  • Peer Reviewed
• [Journal Article] Cyclical and patch-like GDNF distribution along the basal surface of sertoli cells in mouse and hamster testes. (2011)
  • Author(s): T. Sato, Y. Aiyama, M. Ishii-Inagaki, K. Hara, N. Tsunekawa, K. Harikae, M. Uemura-Kamata, M. Shinomura, X. B. Zhu, S. Maeda, et al.
  • Journal Title: PLoS ONE Volume: 6 Issue: 12 Pages: e28367-e28367
  • DOI: 10.1371/journal.pone.0028367
  • Peer Reviewed
• [Journal Article] 分担「生物機能モデルと新しいリソース,リサーチツール (2011)
  • Author(s): 金井
  • Journal Title: series モデル動物利用マニュアル」エル・アイ・ シー Pages: 152-166
• [Journal Article] Sox 17-dependent gene expression and early heart and gut development in Sox 17-deficient mouse embryos. (2011)
  • Author(s): Pfister, et al.
  • Journal Title: Int J Dev Biol Volume: 55 Pages: 45-58
  • Peer Reviewed
• [Journal Article] FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation. (2010)
  • Author(s): Hiramatsu R, Harikae K, Tsunekawa N, Kurohmaru M, Matsuo I, Kanai Y.
  • Journal Title: Development Volume: 137(2) Issue: 2 Pages: 303-312
  • DOI: 10.1242/dev.040519
  • Peer Reviewed
• [Journal Article] Expression and function of mouse Sox17 gene in the specification of gallbladder/bile-duct progenitors during early foregut morphogenesis. (2010)
  • Author(s): Uemura M, Hara K, Shitara H, Ishii R, Tsunekawa N, Miura Y, Kurohmaru M, Taya C, Yonekawa H, Kanai-Azuma M, Kanai Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 391(1) Issue: 1 Pages: 357-363
  • DOI: 10.1016/j.bbrc.2009.11.063
  • Peer Reviewed
• [Journal Article] Expression and function of mouse Sox17 gene in the specification of galbladder/bile-duct progenitors during early foregut morphogenesis (2010)
  • Author(s): Uemura M, et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 391 Pages: 357-363
  • Peer Reviewed
• [Journal Article] FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation. (2010)
  • Author(s): Hiramatsu R, et al.
  • Journal Title: Development Volume: 137 Pages: 303-312
  • Peer Reviewed
• [Journal Article] Expression and function of mouse Sox17 gene in the specification of gallbladder/bile-duct progenitors during early foregut morphogenesis (2010)
  • Author(s): Uemura M, et al.
  • Journal Title: Biochem Biophys Res Commun. 391(1) Pages: 357-363
  • Peer Reviewed
• [Journal Article] Evidence for crucial role of hindgut expansion in directing proper migration of primordial germ cells in mouse early embryogenesis. (2009)
  • Author(s): Hara K, Kanai-Azuma M, Uemura M, Shitara H, Taya C, Yonekawa H, Kawakami H, Tsunekawa N, Kurohmaru M, Kanai Y.
  • Journal Title: Dev Biol Volume: 330(2) Issue: 2 Pages: 427-439
  • DOI: 10.1016/j.ydbio.2009.04.012
  • Peer Reviewed
• [Journal Article] A critical time windows of Sry action in gonadal sex differentiation in mice (2009)
  • Author(s): Hiramatsu R, Matoba S, Kanai-Azuma M, Tsunekawa N, Katoh-Fukui Y, Kurohmaru M, Morohashi K, Wilhelm D, Koopman P, Kanai Y.
  • Journal Title: Development Volume: 36(1) Issue: 1 Pages: 129-138
  • DOI: 10.1242/dev.029587
  • Peer Reviewed
• [Journal Article] The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice (2009)
  • Author(s): Bradford ST, Hiramatsu R, Maddugoda MP, Bernard P, Chaboissier MC, Sinclair A, Schedl A, Harley V, Kanai Y, Koopman P, Wilhelm D.
  • Journal Title: Biol Reprod Volume: 80(6) Issue: 6 Pages: 1178-1188
  • DOI: 10.1095/biolreprod.108.071480
  • Peer Reviewed
• [Journal Article] Evidence for crucial role of hindgut expansion in directing proper migration of primordial germ cells in mouse early embryogenesis. (2009)
  • Author(s): Hara K, et al.
  • Journal Title: Dev Biol 330(2) Pages: 427-439
  • Peer Reviewed
• [Journal Article] The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice. (2009)
  • Author(s): Bradford ST, et al.
  • Journal Title: Biol Reprod 80(6) Pages: 1178-1188
  • Peer Reviewed
• [Presentation] Invited lecture: A gene-dosage function of Sox17 in gallbladder / bile duct morphogenesis, Faculty of Veterinary Technology (2012)
  • Author(s): Kanai Y.
  • Organizer: Kasetsart University
  • Place of Presentation: Bangkok, Tailand
  • Year and Date: 2012-02-28
• [Presentation] Sox-F family proteins have roles in the maintenance of immature phenotypeof the hematopoietic cell clusters in the aorta-gonad mesonephros region of mouse embryo. (2012)
  • Author(s): Nobuhisa I, Osawa M, Uemura M, Kishikawa Y, Anani M, Harada K, Takagi H, Kudo A, Kanai-Azuma M, Kanai Y, Iwama A, Taga T.
  • Organizer: The 10th annual meeting of International Society for Stem Cell Research
  • Place of Presentation: Yokohama
• [Presentation] Hematopoietic cell clusters present in the aorta-gonad-mesonephros region exhibited long-term repopulating ability by Sox17-expression. (2011)
  • Author(s): Nobuhisa I, Osawa M, Uemura M, Kishikawa Y, Anani M, Harada K, Takagi H, Kudo A, Kanai-Azuma M, Kanai Y, Iwama A, Taga T.
  • Organizer: The 35th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Fukuoka
• [Presentation] Heterogeneity in Sexual Bipotentiality and Plasticity of Granulosa Cells in Mouse Ovaries. (2011)
  • Author(s): Kanai Y.
  • Organizer: The 3rd SOX Meeting (organized by Michael Wegner).
  • Place of Presentation: Grainau, Germany
• [Presentation] 性決定遺伝子Sryの時空間的な制御機序 (2010)
  • Author(s): 金井克晃
  • Organizer: 「発生・生殖生物学の最前線」,第51回日本組織細胞化学会シンポジウム.
  • Place of Presentation: 秋葉原コンベンションホール(東京都)
  • Year and Date: 2010-09-05
• [Presentation] 哺乳類の性決定メカニズムの解析 (2009)
  • Author(s): 金井克晃
  • Organizer: 日本農学アカデミー第11回シンポジウム
  • Place of Presentation: 東京大学農学部
  • Year and Date: 2009-11-07
• [Presentation] A gene-dosage function of Sox17 in gallbladder / bile duct morphogenesis
  • Author(s): Yoshiakira Kanai
  • Organizer: Invited lecture: Faculty of Veterinary Technology, Kasetsart University
  • Place of Presentation: Bangkok, Tailand.
  • Invited
• [Book] 生物機能モデルと新しいリソース, リサーチツールseriesモデル動物利用マニュアル (生殖腺の項目 分担執筆) (2011)
  • Author(s): 金井克晃
  • Publisher: エル・アイ・シー
• [Remarks]
  • URL: http://www.vm.a.u-tokyo.ac.jp/kaibo/Sox17.html
• [Remarks] 研究紹介・マウス発生過程におけるSRY関連遺伝子SOX17の機能解析
  • URL: http://www.vm.a.u-tokyo.ac.jp/kaibo/Sox17.html#abc
• [Remarks]
  • URL: http://www.vm.a.u-tokyo.ac.jp/kaibo/Sox17.htmi
• [Remarks]
  • URL: http://www.vm.a.u-tokyo.ac.jp/kaibo/Sox17.html