Gene regulatory network in the epiblast regionalization and somatic lineage derivation

• Project/Area Number: 17H03688
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kyoto Sangyo University
• Principal Investigator: KONDOH Hisato 京都産業大学, 総合学術研究所, 科研費研究員 (70127083)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: エピブラスト / 体細胞発生 / 神経系 / 内胚葉 / 転写因子 / 幹細胞 / ニワトリ胚 / マウス胚 / 領域特性 / 神経幹細胞 / 内胚葉前駆体 / 原腸陥入 / 細胞分化

Outline of Final Research Achievements

Any somatic tissue has its developmental origin in the pluripotent epiblast. We investigated the early stages of somatic tissue development focusing on the neural and endodermal primordia.
Anterior epiblast cells already have regionalities of future brain portions when the node develops. As the epiblast cells gather upon the node-derived anterior mesendoderm, they form the neural primordium already with the traits of brain portions. The higher Wnt signal level in the posterior embryo sites determines the posterior regionality in the hindbrain and spinal cord. Further neural development from the primordium is promoted by cooperative actions of the SOX2 and ZIC2 transcription factors.
Interaction of the SOX17-expressing fraction of the epiblast cells with the laminin-rich basement membrane elicits the genesis of the endodermal primordium. The action of the esophageal SOX2 against the tracheal development is essential for the esophagus/trachea separation in the anterior endoderm.

Academic Significance and Societal Importance of the Research Achievements

ヒトの胚発生では、受精後１ヶ月の間に、エピブラストという体細胞全体の前駆体から様々な体細胞組織の原基が発生し成立する。胚発生の最も重要な時期である。この時期の発生が順調に進行しないと、さまざまな先天異常の原因にもなる。この時期の胚発生の主要なプロセス、ニワトリ胚、マウス胚、マウス胚から樹立したエピブラスト幹細胞株を用いて研究した。

Research Products

• [Int'l Joint Research] Emory University of Medicine(米国)
• [Journal Article] The formation of multiple pituitary pouches from the oral ectoderm causes ectopic lens development in hedgehog signaling-defective avian embryos. (2020)
  • Author(s): Taira Y, Ikuta Y, Inamori S, Nunome M, Nakano M, Suzuki T, Matsuda Y, Tsudzuki M, Teramoto M, Iida H, Kondoh H.
  • Journal Title: Developmental Dynamics Volume: 249 Issue: 12 Pages: 1425-1439
  • DOI: 10.1002/dvdy.222
  • Peer Reviewed / Open Access
• [Journal Article] Modeling early stages of endoderm development in epiblast stem cell aggregates with supply of extracellular matrices. (2020)
  • Author(s): Inamori S, Fujii M, Satake S, Iida H, Teramoto M, Sumi T, Meno C, Ishii Y, Kondoh H.
  • Journal Title: Dev Growth Differ. Volume: － Issue: 4 Pages: 243-259
  • DOI: 10.1111/dgd.12663
  • Peer Reviewed / Open Access
• [Journal Article] Sox2 gene regulation via the D1 enhancer in embryonic neural tube and neural crest by the combined action of SOX2 and ZIC2 (2020)
  • Author(s): Iida Hideaki、Furukawa Yoko、Teramoto Machiko、Suzuki Hitomi、Takemoto Tatsuya、Uchikawa Masanori、Kondoh Hisato
  • Journal Title: Genes to Cells Volume: In press Issue: 4 Pages: 242-256
  • DOI: 10.1111/gtc.12753
  • Peer Reviewed / Open Access
• [Journal Article] The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components (2020)
  • Author(s): Teramoto Machiko、Sugawara Ryo、Minegishi Katsura、Uchikawa Masanori、Takemoto Tatsuya、Kuroiwa Atsushi、Ishii Yasuo、Kondoh Hisato
  • Journal Title: Biology Open Volume: 9 Pages: 048728-048728
  • DOI: 10.1242/bio.048728
  • NAID: 120006859990
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cooperation of Sall4 and Sox8 transcription factors in the regulation of the chicken Sox3 gene during otic placode development (2018)
  • Author(s): Okamoto Yu、Nishimura Naoko、Matsuda Kazunari、Ranawakage Deshani C.、Kamachi Yusuke、Kondoh Hisato、Uchikawa Masanori
  • Journal Title: Development, Growth & Differentiation Volume: 60 Issue: 3 Pages: 133-145
  • DOI: 10.1111/dgd.12427
  • Peer Reviewed / Open Access
• [Journal Article] Roles of ZIC2 in Regulation of Pluripotent Stem Cells (2018)
  • Author(s): Kondoh Hisato
  • Journal Title: Adv Exp Med Biol. Volume: 1046 Pages: 339-351
  • DOI: 10.1007/978-981-10-7311-3_17
  • ISBN: 9789811073106, 9789811073113
  • Peer Reviewed
• [Journal Article] Nasal and otic placode specific regulation of Sox2 involves both activation by Sox-Sall4 synergism and multiple repression mechanisms (2018)
  • Author(s): Sugahara Satoko、Fujimoto Tooru、Kondoh Hisato、Uchikawa Masanori
  • Journal Title: Developmental biology Volume: 433 Issue: 1 Pages: 61-74
  • DOI: 10.1016/j.ydbio.2017.11.005
  • Peer Reviewed
• [Journal Article] Enhancer Analyses Using Chicken Embryo Electroporation (2017)
  • Author(s): Uchikawa Masanori、Nishimura Naoko、Iwafuchi-Doi Makiko、Kondoh Hisato
  • Journal Title: Methods in molecular biology (Clifton, N.J.) Volume: 1650 Pages: 191-202
  • DOI: 10.1007/978-1-4939-7216-6_12
  • ISBN: 9781493972159, 9781493972166
  • Peer Reviewed
• [Journal Article] ChIP-seq analysis of genomic binding regions of five major transcription factors highlights a central role for ZIC2 in the mouse epiblast stem cell gene regulatory network (2017)
  • Author(s): Matsuda Kazunari、Mikami Tomoyuki、Oki Shinya、Iida Hideaki、Andrabi Munazah、Boss Jeremy M.、Yamaguchi Katsushi、Shigenobu Shuji、Kondoh Hisato
  • Journal Title: Development Volume: 144 Pages: 1948-1958
  • DOI: 10.1242/dev.143479
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The formation of multiple pituitary pouches from the oral ectoderm in hedgehog signaling-defective avian embryos causing ectopic lens development (2020)
  • Author(s): Yuki Taira, Yuya Ikuta, Machiko Teramoto, Mitsuo Nunome, Mikiharu Nakano, Takayuki Suzuki, Yoichi Matsuda, Masaoki Tsudzuki, Hideaki Iida, Hisato Kondoh
  • Organizer: 53rd Annual Meeting of JSDB
  • Int'l Joint Research
• [Presentation] Live imaging of avian epiblast development using randomly or selectively marked cell populations (2020)
  • Author(s): Hisato Kondoh, Hideaki Iida, Koya Yoshihi, Kagayaki Kato
  • Organizer: 53rd Annual Meeting of JSDB
  • Int'l Joint Research / Invited
• [Presentation] Possible Sox2 autoregulation involving POU partner factors in the establishment of embryonic neural primordia (2019)
  • Author(s): Hideaki Iida , Masanori Uchikawa, Hisato Kondoh
  • Organizer: 52nd Annunal Meeting of Japanese Society of Developmental Biologists
  • Int'l Joint Research
• [Presentation] Endodermal SOX2 expression determines the esophagus character of the anterior foregut in both epithelial and mesenchymal components (2019)
  • Author(s): Machiko Teramoto, Ryo Sugawara, Atsushi Kuroiwa, Yasuo Ishii, Hisato Kondoh
  • Organizer: 52nd Annunal Meeting of Japanese Society of Developmental Biologists
  • Int'l Joint Research
• [Presentation] A new fate map and anterior mesendoderm-dependent regulation of brain precursor development determined via live imaging of avian embryos (2019)
  • Author(s): Hisato Kondoh, Koya Yoshihi, Hideaki Iida, Machiko Teramoto, Kagayaki Kato
  • Organizer: 52nd Annunal Meeting of Japanese Society of Developmental Biologists
  • Int'l Joint Research
• [Presentation] Changing SOX partners during the developmental progression of stem cells (2019)
  • Author(s): Hisato Kondoh
  • Organizer: Vth International SOX Research Conference
  • Int'l Joint Research / Invited
• [Presentation] 光褪色後蛍光回復法（FRAP）による神経幹細胞内のSOX2のパートナー転写因子との相互作用の解析 (2019)
  • Author(s): 渡邊 優作, 中村 香絵, 三上 智之, 近藤 寿人
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] 単一エンハンサー内でのSOX2-ZIC2、SOX2-PAX3の２つの転写因子相互作用によって、Sox2遺伝子が神経系と神経堤で活性化される (2019)
  • Author(s): 飯田 英明, 内川 昌則, 近藤 寿人
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Modeling node-proximal gastrulation in epiblast stem cells (2019)
  • Author(s): Mai Fujii, Sachiko Inamori, Machiko Teramoto, Hideaki Iida, Hisato Kondoh
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] 食道上皮でのSOX2発現が失われると、上皮だけでなく間充織までも気管と気管支に変わる (2019)
  • Author(s): 寺元 万智子, 菅原 諒, 黒岩 厚, 石井 泰雄, 近藤 寿人
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] A new live imaging technique of avian embryos determining a revised fate map and mesendoderm-dependent gathering of brain precursors (2019)
  • Author(s): Hisato Kondoh, Koya Yoshihi, Machiko Teramoto, Hideaki Iida, Kagayaki Kato
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Mechanisms underlying lens transdifferentiation from neural retina and pituitary (2018)
  • Author(s): Hisato Kondoh
  • Organizer: Gordon Research Conference Visual System Development: Genetics, Genomics, and Evolution of the Eye
  • Int'l Joint Research / Invited
• [Presentation] Live imaging of node graft and host cells to establish its role in head development (2018)
  • Author(s): Koya Yoshihi, Kagayaki Kato, Hisato Kondoh
  • Organizer: Joint Annual Meeting of 51st JSDB and 70th JSCB
  • Int'l Joint Research
• [Presentation] Regulation of a pan-neural Sox2 enhancer D1 (2018)
  • Author(s): Hideaki Iida, Masanori Uchikawa, Hisato Kondoh
  • Organizer: Joint Annual Meeting of 51st JSDB and 70th JSCB
  • Int'l Joint Research
• [Presentation] SOX2-dependent determination of tissue identities in the foregut (2018)
  • Author(s): Machiko Teramoto, Ryo Sugawara, Atsushi Kuroiwa, Yasuo Ishii, Hisato Kondoh
  • Organizer: Joint Annual Meeting of 51st JSDB and 70th JSCB
  • Int'l Joint Research
• [Presentation] The pairing interaction dynamics of the transcription factor SOX2 with partner factors (2018)
  • Author(s): Hisato Kondoh
  • Organizer: International Symposium on “Proteins; from the Cradle to the Grave”
  • Int'l Joint Research / Invited
• [Presentation] Mechanisms underlying lens transdifferentiation in neural retina cells and pituitary precursors (2018)
  • Author(s): Hisato Kondoh
  • Organizer: XXIII Biennial Meeting of the International Society for Eye Research
  • Int'l Joint Research / Invited
• [Presentation] A drastic change in the major regulatory TFs from SOX2- POU5F1 to ZIC2-OTX2 in the pluripotent stem cells representing pre-implantation and post-implantation stages (2018)
  • Author(s): Hisato Kondoh
  • Organizer: EMBO Workshop: Molecular Mechanisms of Developmental and Regenerative Biology
  • Int'l Joint Research / Invited
• [Presentation] D1エンハンサーによる、胚の中枢神経系と頭部神経堤におけるSox2発現の制御 (2018)
  • Author(s): 飯田 英明、内川 昌則、近藤 寿人
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] 内胚葉で発現されるSOX2が前腸の上皮と間充織の双方を食道に発生させる (2018)
  • Author(s): 寺元 万智子、菅原 諒、黒岩 厚、石井 泰雄、近藤 寿人
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] エピブラスト幹細胞を用いて、着床後に体細胞系列が生み出される機構を研究する (2018)
  • Author(s): 近藤 寿人、中村 香絵、渡邊 優作、藤井 麻衣、稲森 祥子、飯田 英明
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] SOX2-dependent determination of tissue identity in the foregut. (2017)
  • Author(s): Teramoto M, Sugawara R, Ishii Y, Kuroiwa A, Kondoh H.
  • Organizer: ConBio2017
• [Presentation] A drastic change in the major regulatory TFs from SOX2-POU5F1 to ZIC2-OTX2 in the pluripotent stem cells representing pre-implantation and post-implantation stages. (2017)
  • Author(s): Kondoh H, Matsuda K, Oki S, Shigenobu S.
  • Organizer: ConBio2017
• [Presentation] エピブラスト幹細胞株から樹立された領域特性をもつ神経幹細胞株の解析 (2017)
  • Author(s): 中村香絵、Boitet C、吉氷康矢、飯田英明、近藤寿人
  • Organizer: ConBio2017
• [Presentation] Foxa2とともにnEGFPを発現するエピブラスト幹細胞を用いた、初期発生過程の研究 (2017)
  • Author(s): 稲森祥子、石井泰雄、近藤寿人
  • Organizer: ConBio2017
• [Presentation] ヘンゼン結節は脊索前板の発生を介して、Otx2を発現するエピブラストに頭部を形成させる (2017)
  • Author(s): 吉氷康矢、近藤寿人
  • Organizer: ConBio2017
• [Presentation] Sox2の神経系での発現を制御するD1エンハンサーの解析 (2017)
  • Author(s): 飯田英明、内川昌則、近藤寿人
  • Organizer: ConBio2017
• [Presentation] SOX2-dependent determination of tissue identity in the foregut. (2017)
  • Author(s): Teramoto M, Sugawara R, Ishii Y, Kuroiwa A, Kondoh H.
  • Organizer: ISDB 2017
  • Int'l Joint Research
• [Presentation] Roles for ZIC2 in the regulation of epiblast stem cells and embryonic stem cells. (2017)
  • Author(s): Kondoh H, Matsuda K, Oki S, Shigenobu S.
  • Organizer: ISDB 2017
  • Int'l Joint Research
• [Presentation] Embryonic region-dependent development and interactions of grafted Hensen’s node with host tissues: reconsideration of organizer model. (2017)
  • Author(s): Kondoh H, Yoshihi K.
  • Organizer: 50th Annual Meeting of the Japanese society of Developmental Biologists.
  • Int'l Joint Research / Invited
• [Presentation] Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of “lens transdifferentiation”. (2017)
  • Author(s): Iida H, Ishii Y, Kondoh H.
  • Organizer: 50th Annual Meeting of the Japanese society of Developmental Biologists.
  • Int'l Joint Research
• [Presentation] Establishment of neural progenitor cells lines with defined regional specificities from EpiSCs. (2017)
  • Author(s): Nakamura K, Boitet C, Satake S, Yoshihi K, Iida H, Ishii Y, Kondoh H.
  • Organizer: 50th Annual Meeting of the Japanese society of Developmental Biologists.
  • Int'l Joint Research
• [Presentation] Establishment and use of a new epiblast stem cell line marking Foxa2 expression with GFP. (2017)
  • Author(s): Inamori S, Ishii Y, Kondoh H.
  • Organizer: 50th Annual Meeting of the Japanese society of Developmental Biologists.
  • Int'l Joint Research
• [Presentation] SOX2-dependent determination of tissue identity in the foregut. (2017)
  • Author(s): Teramoto M, Sugawara R, Ishii Y, Kuroiwa A, Kondoh H.
  • Organizer: 50th Annual Meeting of the Japanese society of Developmental Biologists.
  • Int'l Joint Research
• [Remarks] 再生医療の地図を描くエピブラスト幹細胞
  • URL: https://www.kyoto-su.ac.jp/faculty/professors/nls/ahcetq00000023w2-att/st_kondo.pdf
• [Remarks] Laboratory of Developmental Biology 発生生物学研究室
  • URL: https://www.cc.kyoto-su.ac.jp/~i1659235/HKlab/index.html
• [Remarks] SOX2に導かれた発生の遺伝子制御への道
  • URL: https://www.kyoto-su.ac.jp/graduate/g_ls/kenkyu/kondo.html
• [Remarks] 教員紹介 教授 近藤寿人
  • URL: https://www.kyoto-su.ac.jp/graduate/g_ls/kyoin/kondo.html