Molecular mechanisms of lamina-specific neural circuit formation in the neocortex

新皮质层层特异性神经回路形成的分子机制

基本信息

批准号：
15300107
负责人：
YAMAMOTO Nobuhiko
金额：
$ 10.62万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The cerebral cortex is composed of six cell layered structure, by which neural connections are established. As such laminar structure is present in not only the cerebral cortex but also other central nervous systems, it is thought to be a principle for neural circuit formation. To date, developmental studies in vivo and in vitro studies including ours (Yamamoto et al, 1989,1992,1995,1997) have demonstrated that each layer cells have specific target recognition mechanisms to produce afferent and efferent connections. Moreover, the mechanisms are regulated by the molecules that are expressed in a lamina-specific fashion (Yamamoto et al, 2000a,b). However, the presence and function of these lamina-specific molecules were not almost unknown.In this study, we attempted to identify these lamina-specific molecules, and to reveal the involvement of them in cortical circuit formation. To do that, a subtraction cDNA library was constructed by extracting RNAs from each layer, and were applied to screening lamina-specific genes. As a result, several genes which code transcription factors and cell surface molecules were identified as layer 4 or layer 5-specific molecules. Moreover, a lamina-specific molecule, which belongs to cadherin family, was obtained by using monoclonal antibody technique. We suggested that these lamina-specific genes may be involved in cell type specification and cortical circuit formation by analyzing developmental expression patterns and relation between gene expression and cell types.

大脑皮层由六细胞分层结构组成，通过它建立神经连接。由于这种层状结构不仅存在于大脑皮层中，而且还存在于其他中枢神经系统中，因此它被认为是神经回路形成的原理。迄今为止，包括我们在内的体内和体外发育研究（Yamamoto et al, 1989,1992,1995,1997）已经证明，每一层细胞都有特定的目标识别机制来产生传入和传出连接。此外，该机制受到以层板特异性方式表达的分子的调节（Yamamoto 等人，2000a，b）。然而，这些层特异性分子的存在和功能并非几乎未知。在这项研究中，我们试图识别这些层特异性分子，并揭示它们在皮质回路形成中的参与。为此，通过从每一层中提取RNA来构建消减cDNA文库，并将其用于筛选核纤层特异性基因。结果，编码转录因子和细胞表面分子的几个基因被鉴定为第4层或第5层特异性分子。此外，利用单克隆抗体技术获得了属于钙粘蛋白家族的核纤层特异性分子。通过分析发育表达模式以及基因表达与细胞类型之间的关系，我们认为这些层特异性基因可能参与细胞类型规范和皮质回路形成。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

BDNF and NT-3 promote thalamocortical axon growth with distinct substrate and temporal dependency

DOI：
10.1111/j.1460-9568.2004.03228.x
发表时间：
2004-03-01
期刊：
EUROPEAN JOURNAL OF NEUROSCIENCE
影响因子：
3.4
作者：
Hanamura, K;Harada, A;Yamamoto, N
通讯作者：
Yamamoto, N

Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate neocortices

DOI：
10.1016/j.neuroscience.2005.08.075
发表时间：
2006-12
期刊：
Neuroscience
影响因子：
3.3
作者：
H. Yoneshima;S. Yamasaki;C. Voelker;Z. Molnár;E. Christophe;E. Audinat;M. Takemoto;M. Nishiwaki;S. Tsuji;I. Fujita;N. Yamamoto
通讯作者：
H. Yoneshima;S. Yamasaki;C. Voelker;Z. Molnár;E. Christophe;E. Audinat;M. Takemoto;M. Nishiwaki;S. Tsuji;I. Fujita;N. Yamamoto

Identification of the genes that are expressed in the upper layers of the neocortex.

DOI：
10.1093/cercor/bhh074
发表时间：
2004-10
期刊：
Cerebral cortex
影响因子：
3.7
作者：
Yun Zhong;M. Takemoto;Tsuyoshi Fukuda;Yuki Hattori;F. Murakami;D. Nakajima;M. Nakayama;N. Yamamoto
通讯作者：
Yun Zhong;M. Takemoto;Tsuyoshi Fukuda;Yuki Hattori;F. Murakami;D. Nakajima;M. Nakayama;N. Yamamoto

Identification of the genes that are expressed in the upper lavers of the neocortex.

鉴定在新皮质上层表达的基因。