Principle of organogenesis derived from neural crest cells

• Project/Area Number: 18390061
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Jichi Medical University
• Principal Investigator: KAWAKAMI Kiyoshi Jichi Medical University, 医学部, 教授 (10161283)
• Co-Investigator(Kenkyū-buntansha): YAJIMA Hiroshi 自治医科大学, 医学部, 講師 (10433583) ; IKEDA Keiko 自治医科大学, 医学部, 准教授 (10265241)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,060,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥2,460,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2006: ¥6,400,000 (Direct Cost: ¥6,400,000)
• Keywords: 神経堤細胞 / 脳神経節 / 脊髄神経節 / Six1 / Six4 / 遺伝子欠損マウス / トランスジェニックマウス / 発生と分化 / 一次感覚神経

Research Abstract

神経堤細胞系譜がmRFP で特異的に標識されたマウスを構築できた。このマウスを用いてSix1/Six4 二重欠損マウスの神経管の中に異所的に生じる一次感覚神経細胞が、神経堤細胞由来であることを明らかにした。この細胞は、神経管のなかに存在する一次感覚神経細胞である無羊膜類のRohon-Beard 細胞とよく似ていた。従ってSix1 およびSix4 は一次感覚神経の脊髄内および脊髄外の局在を制御する働きがある事が示唆された。また、Six1/Six4 二重欠損マウスの脊髄神経節に存在する神経細胞には分化異常が観察された。
Six1/Six4 二重欠損マウスの鼻プラコードにおいては、アポトーシスの有意な増加は認められなかったが、細胞増殖は顕著に低下していた。従って、鼻プラコードの形成不全の原因のひとつは細胞増殖の低下であった。
Six1/Six4 二重欠損マウスの鼻プラコードにおいては、アポトーシスの有意な増加は認められなかったが、細胞増殖は顕著に低下していた。従って、鼻プラコードの形成不全の原因のひとつは細胞増殖の低下であった。
比較ゲノム解析とニワトリ胚へのエレクトロポレーションにより、Six1 およびEya1 遺伝子周辺の塩基配列から、Six1 で8 箇所、Eya1 で10 箇所の特異的なエンハンサーを同定した。これらの活性をあわせると、内在性のSix1 とEya1 の発現をほぼ再現できた。Six1 の耳プラコードエンハンサーではSix1 自身の自己制御が示唆された。また、PPR エンハンサーではホメオボックスおよびGATA 結合配列が重要であった。PPR の生ずる神経板周辺で発現するDlx5 やDlx6がエンハンサーを活性化する可能性が示唆された。
Six1/Six4 二重欠損マウスと野生型との遺伝子発現の比較は、脊髄神経節を単離して行った。詳しい検討は今後行う予定である。

Research Products

• [Journal Article] The Six1 homeobox gene is critical for proliferation in the developing mouse submandibular salivary gland. (2009)
  • Author(s): Mccoy, E.L., Kawakami, K., Ford, H. L., and Coletta, R.D.
  • Journal Title: Oral Diseases in press
  • Peer Reviewed
• [Journal Article] The Six1 homeobox gene is critical for proliferation in the developing mouse submandibular salivary gland. (2009)
  • Author(s): Mccoy, E. L.
  • Journal Title: Oral Diseases (In press)
  • Peer Reviewed
• [Journal Article] Multiple Evolutionarily Conserved Enhancers Control Expression of Eya1. (2008)
  • Author(s): Ishihara, T., Sato, S., Ikeda, K., Yajima, H., and Kawakami, K.
  • Journal Title: Dev. Dyn. 237 Pages: 3142-3156
  • Peer Reviewed
• [Journal Article] Differential expression of Eya1 and Eya2 during chick early embryonic development. (2008)
  • Author(s): Ishihara, T., Ikeda, K., Sato, S., Yajima, H., and Kawakami, K.
  • Journal Title: Gene Exp. Patterns 8 Pages: 357-367
  • Peer Reviewed
• [Journal Article] Differential expression of Eya1 and Eya2 during chick early embryonic development. (2008)
  • Author(s): Ishihara, T.
  • Journal Title: Gene Exp. Patterns 8 Pages: 357-367
  • Peer Reviewed
• [Journal Article] Multiple Evolutionarily Conserved Enhancers Control Expression of Eya1. (2008)
  • Author(s): Ishihara, T.
  • Journal Title: Dev. Dyn. 237 Pages: 3142-3156
  • Peer Reviewed
• [Journal Article] Six1 is essential for early neruogenesis in the development of olfactory epithelium. (2007)
  • Author(s): Ikeda, K., Ookawara, S., Sato, S., Ando, Z., Kageyema, R. and Kawakami, K.
  • Journal Title: Dev. Biol. 311 Pages: 53-68
  • Peer Reviewed
• [Journal Article] Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric tubule defects. (2007)
  • Author(s): Kobayashi, H., Kawakami, K., Asashima, M. and Nishinakamura, R.
  • Journal Title: Mech. Dev. 124 Pages: 290-303
  • Peer Reviewed
• [Journal Article] Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric tubule defects. (2007)
  • Author(s): Kobayashi, H.
  • Journal Title: Mech. Dev. 124 Pages: 290-303
  • Peer Reviewed
• [Journal Article] Six1 is essential for early neruogenesis in the development of olfactory epithelium. (2007)
  • Author(s): Ikeda, K.
  • Journal Title: Dev. Biol. 311 Pages: 53-68
  • Peer Reviewed
• [Journal Article] Differential expression of Eya1 and Eya2 during chick early embryonic development. (2007)
  • Author(s): Ishihara, T.
  • Journal Title: Gene Exp. Patterns
  • Peer Reviewed
• [Journal Article] Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis. (2006)
  • Author(s): Konishi, Y., Ikeda, K., Iwakura, Y. and Kawakami, K.
  • Journal Title: Brain Res. 1116 Pages: 93-102
  • Peer Reviewed
• [Journal Article] Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development. (2006)
  • Author(s): Chai, L., Yang, J., Di, C., Cui, W., Kawakami, K., Lai, R. and Ma, Y.
  • Journal Title: J. Biol. Chem. 281 Pages: 18918-18926
  • Peer Reviewed
• [Journal Article] Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development. (2006)
  • Author(s): Chai, L.
  • Journal Title: J. Biol. Chem. 281 Pages: 18918-18926
• [Journal Article] Six1 and Six4 promote survival of sensory neurons during eary trigeminal gangliogenesis. (2006)
  • Author(s): Konishi, Y.
  • Journal Title: Brain Res. 1116 Pages: 93-102
• [Journal Article] Divergent signaling pathways mediate induction of Na, K-ATPase α1 and β1 subunit gene transcriotion by low potassium. (2006)
  • Author(s): Wang, G.
  • Journal Title: Mol. Cell. Biochem. 294 Pages: 73-85
• [Presentation] Identification of mouse Eya1 enhancers.(講演要旨集: p.455) (2008)
  • Author(s): Ishihara, T., Sato, S., Ikeda, K., Yajima, H., Kawakami, K.
  • Organizer: 第31 回日本分子生物学会年会第81 回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Evolution of preplacodal region and sensory placodes.(Abstracts: p.122) (2008)
  • Author(s): Sato, S., Ikeda, K., Hayashibara, Y., Nakao, K., Aizawa, S., Kawakami, K.
  • Organizer: The 16^<th> CDB Meeting
  • Place of Presentation: Kobe
• [Presentation] Early neurogenesis in the development of olfactory epithelium.(Neuroscience Research, Volume 61, Supplement 1, S23) (2008)
  • Author(s): Ikeda, K., Kawakami, K.
  • Organizer: The 31^<st> Annual Meeting of The Japan Neuroscience Society
  • Place of Presentation: Tokyo
• [Presentation] Evolution of Six1 enhancers in vertebrates.(Program and Abstract Book: p.206) (2008)
  • Author(s): Sato, S., Ikeda, K., Nakayama, R., Bunno, T., Hayashibara, Y., Aizawa, S., Kawakami, K
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Expression patterns of Eya1 and Eya2 in chick early development.(Program and Abstract Book: p.212) (2008)
  • Author(s): Ishihara, T., Ikeda, K., Sato, S., Yajima, H., Kawakami, K.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Role of Six1 and Six4 in cranial gangliogenesis.(Program and Abstract Book: p.181) (2008)
  • Author(s): Ikeda, K., Yajima, H., Yamakado, M., Kawakami, K.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Hidden developmental program of Rohon-Beard cells in mice.(Program and Abstract Book: p.180) (2008)
  • Author(s): Yajima, H., Ikeda, K., Sato, S., Kawakami, K.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Pioneer neurons in early neurogenesis of olfactory epithelium.(Abstracts: p.52) (2008)
  • Author(s): Ikeda, K., Kawakami, K.
  • Organizer: Brain Development Symposium
  • Place of Presentation: London
• [Presentation] 舌乳頭形成におけるSix4 遺伝子の発現(抄録:p.240) (2008)
  • Author(s): 鈴木裕子、池田啓子、川上潔
  • Organizer: 第113 回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大分
• [Presentation] Pioneer neurons in early neurogenesis of olfactory epithelium. (2008)
  • Author(s): Ikeda, K.
  • Organizer: Brain Development Symposium
  • Place of Presentation: London
• [Presentation] Hidden developmental program of Rohon-Beard cells in mice. (2008)
  • Author(s): Yajima, H.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Role of Six1 and Six4 in cranial gangliogenesis. (2008)
  • Author(s): Ikeda, K.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Evolution of Six1 enhancers in vertebrates. (2008)
  • Author(s): Sato, S.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Expression patterns of Eya1 and Eya2 in chick early development. (2008)
  • Author(s): Ishihara, T.
  • Organizer: 41st Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Tokushima
• [Presentation] Early neurogenesis in the development of olfactory epithelium. (2008)
  • Author(s): Ikeda, K.
  • Organizer: The 31st Annual Meeting of The Japan Neuroscience Society
  • Place of Presentation: Tokyo
• [Presentation] Evolution of preplacodal region and sensory placodes. (2008)
  • Author(s): Sato, S.
  • Organizer: The 16th CDB Meeting
  • Place of Presentation: Kobe
• [Presentation] Role of Six1 and Six4 in the development of cranial ganglia. (2008)
  • Author(s): Ikeda, K.
  • Organizer: The 9th International Congress on Cell Biology & The 20th Annual Conference of Korean Society for Molecular Biology
  • Place of Presentation: Seoul
• [Presentation] Identification of mouse Eya1 enhancers. (2008)
  • Author(s): Ishihara, T.
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会合同大会
  • Place of Presentation: Kobe
• [Presentation] 舌乳頭形成におけるSix4遺伝子の発現. (2008)
  • Author(s): 鈴木 裕子
  • Organizer: 第113回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大分
• [Presentation] 感覚器の発生を司るホメオボックス転写因子Sixの役割. (2007)
  • Author(s): 川上 潔
  • Organizer: 第2期ハイテク・リサーチ・センター整備事業分子病態治療研究センター開設10周年記念合同シンポジウム
  • Place of Presentation: 栃木
  • Year and Date: 2007-07-21
• [Presentation] 舌乳頭形成に関わるSix1 遺伝子(プログラム・予稿集:p.75) (2007)
  • Author(s): 鈴木裕子、池田啓子、川上潔
  • Organizer: 日本味と匂学会第41 回大会
  • Place of Presentation: 東京
• [Presentation] Roles of Six genes in the proliferation and differentiation of muscle satellite cells.(要旨集:p.183) (2007)
  • Author(s): Yajima, H., Sato, S., Ikeda, K., Miyamoto, K., Masuda, S., Motohashi, N., Yada, E., Suzuki, Y., Takeda, S., Kawakami, K
  • Organizer: 第40 回日本発生生物学会 第59 回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Placode enhancers of the mouse Six1 gene - in vivo analysis using chick and mouse embryos.(要旨集: p.93) (2007)
  • Author(s): Sato, S., Nakayama, R., Ikeda, K., Hayashibara, Y., Nakao, K., Aizawa, S., Kawakami, K.
  • Organizer: 第40回日本発生生物学会 第59 回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Role of Six1 in established neurogenesis of olfactory epithelium development.(要旨集: p.93) (2007)
  • Author(s): Ikeda, K., Kawakami, K.
  • Organizer: 第40 回日本発生生物学会 第59 回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Six1 is necessary for generation of pioneer neurons and olfactory sensory neuron precursors in olfactory epithelium.(要旨集: p.62) (2007)
  • Author(s): Ikeda, K., Ookawara, S., Kawakami, K.
  • Organizer: 第40 回日本発生生物学会第59 回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Six1 is essential for early neurogenesis in olfactory epithelium development.(Abstracts: p.32) (2007)
  • Author(s): Ikeda, K., Kawakami, K., Kageyama.
  • Organizer: Neurogenesis 2007
  • Place of Presentation: Tokyo
• [Presentation] 感覚器形成を司るホメオボックス転写因子Six の役割(学術講演要旨集:p.101) (2007)
  • Author(s): 川上潔、池田啓子、佐藤滋、矢嶋浩、鈴木裕子
  • Organizer: 第27 回日本医学会総会
  • Place of Presentation: 大阪
• [Presentation] 味蕾と舌乳頭形成におけるSix遺伝子の発現(Acta Anatomica Nipponica, Vol.82:p.263) (2007)
  • Author(s): 鈴木裕子、池田啓子、川上潔、瀬田祐司、豊島邦昭
  • Organizer: 第112 回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大阪
• [Presentation] 鰓弓神経発生におけるSix 遺伝子の役割(Acta Anatomica Nipponica, Vo. 82: p.213) (2007)
  • Author(s): 山門誠、大河原重雄、川上潔、池田啓子
  • Organizer: 第112 回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大阪
• [Presentation] Six1 is required for generation of pioneer neurons and olfactory sensory neuron precursors in olfactory epithelium.(Abstracts : p.112) (2007)
  • Author(s): Ikeda, K., Ookawara, S., Kawakami, K.
  • Organizer: UK-APDBN Joint Meeting
  • Place of Presentation: Kobe
• [Presentation] 感覚器形成を司るホメオボックス転写因子Sixの役割. (2007)
  • Author(s): 川上 潔
  • Organizer: 第27回日本医学会総会
  • Place of Presentation: 大阪
• [Presentation] Six1 is essential for early neurogenesis in olfactory epithelium development. (2007)
  • Author(s): Ikeda, K.
  • Organizer: Neurogenesis2007
  • Place of Presentation: 東京
• [Presentation] Six1 is necessary for generation of pioneer neurons and olfactory sensory neuron precursors in olfactory epithelium. (2007)
  • Author(s): Ikeda, K.
  • Organizer: 第40回日本発生生物学会第59回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Role of Six1 in established neurogenesis of olfactory epithelium development. (2007)
  • Author(s): Ikeda, K.
  • Organizer: 第40回日本発生生物学会第59回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Six1 is essential for earlyneurogenesis in the development of olfactory epithelium (2007)
  • Author(s): Ikeda, K.
  • Organizer: Gordon Research Conference
  • Place of Presentation: Andover
• [Presentation] 舌乳頭形成に関わるSix1遺伝子. (2007)
  • Author(s): 鈴木 裕子
  • Organizer: 日本味と匂学会第41回大会
  • Place of Presentation: 東京
• [Presentation] Roles of Six1 and Six4 in development of cranial ganglia.(Abstracts : P34) (2006)
  • Author(s): Yamakado, M., Ando, Z., Kawakami, K., Ikeda, K.
  • Organizer: 16th Biennial Meeting of the International Society of Developmental Neuroscience
  • Place of Presentation: Alberta
• [Presentation] Six1 is a key regulator of multiple cell type differenrtiation in olfactory epithelium.(Abstracts : P33) (2006)
  • Author(s): Ikeda, K., Ando, Z., Kageyama, R., Kawakami, K.
  • Organizer: 16th Biennial Meeting of the International Society of Developmental Neuroscience
  • Place of Presentation: Alberta
• [Presentation] Molecular dissection of the placode specific gene expression. (Abstracts : p.307) (2006)
  • Author(s): Sato, S., Ishihara, T., Kawakami, K.
  • Organizer: European Society for Evolutionary Developmental Biology,The First and Founding Meeting
  • Place of Presentation: Prague
• [Presentation] Six1 and Six4 cooperatively function in the nephrogenic mesenchyme development.(Abstracts : p. 745) (2006)
  • Author(s): Kobayashi, H., Kawakami, K., Asashima,M., Nishinakamaru, R.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto
• [Presentation] Development of mouse olfactory epithelium.(Abstracts : p. 544) (2006)
  • Author(s): Ikeda, K., Ando, Z., Ookawara, S., Kageyama, R., Kawakami, K.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto
• [Presentation] :脳神経節におけるSix 遺子の役割(発表要旨集:p.177) (2006)
  • Author(s): 山門誠、安藤善一、大河原重雄、川上潔、池田啓子
  • Organizer: 日本発生生物学会第39 回大会
  • Place of Presentation: 広島
• [Presentation] Molecular dissection of Six1 placode enhancers.(発表要旨集:p.148) (2006)
  • Author(s): 佐藤滋、石原忠、川上潔
  • Organizer: 日本発生生物学会第39 回大会
  • Place of Presentation: 広島
• [Presentation] Six1 は嗅上皮における種々の細胞の分化を司る転写因子である(発表要旨集:p.190) (2006)
  • Author(s): 池田啓子、安藤善一、川上潔
  • Organizer: 日本発生生物学会第39 回大会
  • Place of Presentation: 広島
• [Presentation] Role of Six1 and Six4 in the development of cranial ganglia.(Abstracts: p.320)
  • Author(s): Ikeda, K., Yajima, H., Kawakami, K.
  • Organizer: The 9^<th> International Congress on Cell Biology & The 20^<th> Annual Conference of Korean Society for Molecular Biology
  • Place of Presentation: Seoul
• [Remarks]
  • URL: http://www.jichi.ac.jp/biol/home.html
• [Remarks]
  • URL: http://www.jichi.ac.jp/biol/home.html