小脳興奮性ニューロン群の個性決定機構の解析

小脑兴奋性神经元群的人格决定机制分析

• 批准号: 20700282
• 负责人: 川内 大輔
• 金额: $ 2.83万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20700282/
• 关键词: 遺伝子; 神経科学; 小脳; 発現制御; 脳・神経; 発生・分化; ホメオボックス; 顆粒細胞

無脊椎動物から高等脊椎動物まで広く保存されているプロニューラル因子は神経分化開始のスイッチとして機能する。しかし、これら因子が制御する遺伝子に関する知見は未だ乏しい。本研究では、小脳興奮性ニューロンである小脳核ニューロンと小脳顆粒細胞が共通のプロニューラル因子Math1の下流で異なる個性をどのように獲得するか、その解明を目指す。今年度は、交付申請書の研究実施計画に沿って、小脳興奮性ニューロン群の解剖学的知見を得るとともに、プロニューラル因子Math1と小脳興奮性ニューロンに特異的に発現するホメオボックス遺伝子Mbh2の間の遺伝学的な関係を明らかにした。1) 小脳興奮性ニューロンの標識と発達の解析電気穿孔法を用いてレポーター遺伝子EYFPを小脳神経前駆細胞に導入して、小脳核ニューロンおよび小脳顆粒細胞を標識することにより、遺伝子導入時期に依存して標識ニューロンの種類や移動距離・経路が異なることがわかった。2) Mbh2の発現制御機構の解析Math1 siRNAs を生体内電気穿孔法で小脳興奮性ニューロンに導入した結果、Math1の発現低下に伴いMbh2の発現が消失した。逆にMath1の強制発現はMbh2の発現を誘導する。また免疫クロマチン沈降法を用いて、Math1がMbh2ゲノム領域に結合することを示した。以上の結果から小脳においてMbh2がMath1の標的遺伝子であることが明らかとなった(Kawauchi and Saito, 2008)。現在Mbh2遺伝子にLacZを付与したレポーター遺伝子を用い、小脳核ニューロンあるいは小脳顆粒細胞特異的なMbh2エンハンサーを解析中である。3) Math1依存的分化カスケードの更なる同定申請者は別の研究でMbh1、Mbh2の下流候補遺伝子を脊髄において同定しており(投稿準備中)、その結果を踏まえ、現在小脳において解析中である。

The animal of the spine begins to differentiate between the animals of the higher spine and the body of the vertebrae. You know, you don't need a lot of money. In this study, we did a lot of research in this study. In this study, we did a lot of work in this study. In this study, we did a lot of work in this study. In this study, we did a lot of work in this study. in this study, we did a lot of work in this study. in this study, we did a lot of work in this study. in this study, we did a lot of work in this study. in this study, we did a lot of research. This year, the application for the study was carried out to study the anatomy of this year's clinical application program. The results of this year's study were based on the knowledge of the anatomy of this year's clinical study. This year, the application for this year's application study was carried out in this year's application study. The results of this year's study and delivery of this year's application for the study of the anatomy of this year's clinical study and delivery of this year's application for the study of the anatomy of this year's clinical study and delivery of this year's application for the study of the anatomy of this year's clinical study and delivery of this year's application for the study of the anatomy of the population along the trail and in the small body of the body, this year's application study was conducted in this year's study. 1) the computer punch method is used to analyze the identification of the label of the computer. The computer punch method is used to use the cell of the EYFP to register, the cell of the cell to register, the label of the cell to know that the label is registered, the label of the dependent label, the label of the computer, and the movement of the label to move away from the phone. 2) the Mbh2 computer system analyzed the results of the in vivo computer piercing method for Math1 siRNAs students. The results showed that Math1 was low and Mbh2 was found to be missing. Reverse the Math1 command to force the Mbh2 command to be implemented. The immune Mbh2 sedimentation method was used to show the immune response in combination with the field of immunity, Math1 and sedimentation methods. The above results show that the children of Mbh2 Math1 patients are not aware of the details of the diagnosis (Kawauchi and Saito, 2008). It is now in the process of analyzing the characteristics of the Mbh2, which is used in the analysis of the Mbh2 and the cell characteristics of the small nucleus. 3) the differentiation of Math1 dependencies is more important than that of the applicant to study the Mbh1, the Mbh2, the lower waiting list, the lower waiting list, the lower end of the waiting list, the preparation of the submission, the results of the application, and now the decision is in the process of analysis.

项目成果

Transcriptional cascade from Mathl to Mbhl and Mbh2 is required for cerebellar granule cell differentiation

小脑颗粒细胞分化需要从 Mathl 到 Mbhl 和 Mbh2 的转录级联

• 发表时间: 2008
• 期刊: Developmental Biology 322(2)
• 作者: Nemoto W;Toh H.;Daisuke KAWAUCHI
• 通讯作者: Daisuke KAWAUCHI

小脳ニューロンの個性決定に関わる転写因子間の相互抑制

参与决定小脑神经元个体性的转录因子之间的相互抑制

• 发表时间: 2008
• 作者: 川内大輔;斎藤哲一郎
• 通讯作者: 斎藤哲一郎