Analysis of the mechanisms underlying the layer- and region-specificity during brain development

大脑发育过程中层和区域特异性的机制分析

• 批准号: 23500390
• 负责人: OHTSUKA TOSHIYUKI
• 金额: $ 3.33万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23500390/
• 关键词: 脳形態形成; 神経幹細胞; 神経発生; 転写因子; 発生・分化; 脳・神経; 神経科学; 再生医学; 幹細胞

We analyzed the stage- and region-specific gene expression in neural stem cells during cortical development. We performed the functional analysis of Hbp1 that is highly expressed during the neurogenic stages, and found the abnormal brain morphogenesis including enlarged ventricles and thinner cortex in the Hbp1 conditional knockout mice. In the transgenic mice in which Hes1 expression is controlled by the Tet-On system, persistent high expression of Hes1 led to the maintenance of neural stem cells and the expansion of neural stem cell pool in embryonic, postnatal and adult brains. The number of Tbr2-positive intermediate progenitor cells was decreased in the cortical region, and it was found that the superficial layer is thinner and the generation of superficial layer neurons was decelerated and prolonged.

我们分析了皮质发育过程中神经干细胞的阶段和区域特异性基因表达。我们对神经源性阶段高表达的Hbp1进行了功能分析，发现Hbp1条件敲除小鼠的大脑形态发生异常，包括脑室扩大和皮质变薄。在 Hes1 表达受 Tet-On 系统控制的转基因小鼠中，Hes1 的持续高表达导致胚胎、出生后和成年大脑中神经干细胞的维持和神经干细胞池的扩大。皮层区Tbr2阳性中间祖细胞数量减少，表层变薄，表层神经元生成减慢、延长。

项目成果

神経幹細胞における遺伝子発現プロファイルングおよび大脳皮質形成過程における神経分化制御因子の同定

神经干细胞的基因表达谱和大脑皮层形成过程中神经分化调节因子的鉴定

• 发表时间: 2011
• 作者: 大塚俊之;他6名
• 通讯作者: 他6名

Overexpression of Hes1 Leads to Decelerated Timing of Cortical Neurogenesis and Expansion of Neural Stem Cell Reservoir in Postnatal Brain

Hes1 过度表达导致出生后大脑皮层神经发生时间减慢和神经干细胞库扩张

• 发表时间: 2013
• 作者: Toshiyuki Ohtsuka;Ryoichiro Kageyama
• 通讯作者: Ryoichiro Kageyama

神経発生過程における遺伝子発現ダイナミクスによる神経分化制御機構の解明

阐明神经发生过程中通过基因表达动态控制神经元分化的机制

• 发表时间: 2013
• 作者: 下條博美;播磨有希子;前田勇樹;大塚俊之;他2名
• 通讯作者: 他2名

Gene Expression Profiling of Neural Stem Cells and Identification of Regulators of Neural Differentiation During Cortical Development

• DOI: 10.1002/stem.731
• 发表时间: 2011-11-01
• 期刊: STEM CELLS
• 影响因子: 5.2
• 作者: Ohtsuka, Toshiyuki;Shimojo, Hiromi;Kageyama, Ryoichiro
• 通讯作者: Kageyama, Ryoichiro

Continuous neurogenesis in the adult forebrain is required for innate olfactory responses

• DOI: 10.1073/pnas.1018782108
• 发表时间: 2011-05-17
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Sakamoto, Masayuki;Imayoshi, Itaru;Kageyama, Ryoichiro
• 通讯作者: Kageyama, Ryoichiro