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Potential of neural stem cells during development.

神经干细胞在发育过程中的潜力。

基本信息

批准号：
15609002
负责人：
SAITO Tetsuichiro
金额：
$ 1.98万
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：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The mammalian cerebral cortex is comprised of six layers of neurons. Cortical progenitors in the ventricular zone generate neurons specific to each layer through successive cell divisions. Neurons of layer VI are generated at an early stage, whereas later-born neurons occupy progressively upper layers. Its underlying molecular mechanisms are little known. In this study, we devised a system where the Notch pathway was activated spatiotemporally in the cortex by in vivo electroporation and Cre-mediated DNA recombination. Electroporation at E13.5 transferred DNA to early progenitors that gave rise to neurons of both low and upper layers. Forced expression of a constitutively active form of Notch (caNotch) at E13.5 inhibited progenitors from generating neurons and kept progenitors as proliferating radial glial cells. After subsequent transfection at E15.5 of a Cre expression vector to remove caNotch, double-transfected cells, where caNotch was excised, migrated into the cortical plate and differentiated into neurons specific to upper layers. Bromodeoxyuridine-labeling experiments showed that the neurons were born after Cre transfection. These results indicate that cortical progenitors that had been temporarily subjected to Notch activation at an early stage generated neurons at later stages, but that the generation of low-layer neurons was skipped. Moreover, the double-transfected cells gave rise to upper-layer neurons, even after their transplantation into the E13.5 brain, indicating that the developmental state of progenitors is not halted by caNotch activity.

哺乳动物大脑皮层由六层神经元组成。心室区的皮质祖细胞通过连续的细胞分裂产生每一层特有的神经元。 VI 层的神经元是在早期产生的，而后来产生的神经元逐渐占据上层。其潜在的分子机制鲜为人知。在这项研究中，我们设计了一个系统，通过体内电穿孔和 Cre 介导的 DNA 重组，在皮质中时空激活 Notch 通路。 E13.5 的电穿孔将 DNA 转移到早期祖细胞中，从而产生下层和上层神经元。在 E13.5 处强制表达 Notch (caNotch) 的组成型活性形式可抑制祖细胞生成神经元，并使祖细胞保持增殖的放射状胶质细胞。随后在 E15.5 处转染 Cre 表达载体以去除 caNotch，双转染细胞（caNotch 被切除）迁移到皮质板中并分化为上层特异的神经元。溴脱氧尿苷标记实验表明，Cre 转染后神经元诞生。这些结果表明，在早期阶段暂时受到Notch激活的皮层祖细胞在后期产生了神经元，但跳过了低层神经元的产生。此外，即使在移植到 E13.5 大脑中之后，双转染的细胞也会产生上层神经元，这表明祖细胞的发育状态不会因 caNotch 活性而停止。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chiung-Wen Chang: "Identification of a developmentally regulated striatum-enriched zinc-finger gene, Nolz-1, in the mammalian brain"Proc.Nail.Acad.Sci.USA. 101. 2613-2618 (2004)

Chiung-Wen Chang：“哺乳动物大脑中发育调节纹状体富集的锌指基因 Nolz-1 的鉴定”Proc.Nail.Acad.Sci.USA。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Commissural neuron identity is specified by a homeodomain protein, MBH1,directly downstream of Math1.

连合神经元的身份由同源域蛋白 MBH1 指定，该蛋白直接位于 Math1 的下游。

DOI：
发表时间：
2005
期刊：
Development (印刷中)
影响因子：
0
作者：
Ban;T.et al.;Toyoda H. et al.;Ueta Y.et al.;Inoue K. et al.;Wang C.et al.;Inoue K. et al.;Yamada J. et al.;Uchida K. et al.;Ikeda K. et al.;福田敦夫;Ken-ichi Mizutani;Rie Saba
通讯作者：
Rie Saba

The Sox-2 regulatory regions display their activities in two distinct multipotent stem cells.

Sox-2 调节区在两种不同的多能干细胞中显示出其活性。

DOI：
发表时间：
2004
期刊：
Mol.Cell.Biol. 24
影响因子：
0
作者：
Ken-ichi Mizutani;Rie Saba;Ken-ichi Mizutani;Rie Saba;Ken-ichi Mizutani;Rie Saba;Satoru Miyagi;Satoru Miyagi
通讯作者：
Satoru Miyagi

Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral cortex