Cellular and molecular functions and signalling mechanisms of Nel

Nel的细胞分子功能及信号机制

• 批准号: BB/G007632/1
• 负责人: Masaru Nakamoto
• 金额: $ 71.79万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG007632%2F1
• 关键词: Cellular; molecular; functions; signalling; mechanisms

The brain contains an orderly and stereotyped network of nerve cells, and correct functioning of the brain is critically dependent on the proper formation of the neuronal network. In human, for example, it is estimated that about one billion nerve cells form more than one quadrillion specific connections. During development of the neuronal network, nerve fibres must follow the defined pathways and project to the correct targets. In this process, nerve fibres are guided by external molecular cues derived from their pathways and targets. Guidance cues are recognized by nerve fibres through specific 'receptors'. Therefore, studies on the interaction between guidance molecules and their receptors are a key to the elucidation of molecular mechanisms of brain development. The proposed research focuses on a protein called Nel. Although Nel exists in the developing nervous system and has structural features that are found in other molecules that play important biological functions, little is known about its functions in development of the nervous system. In addition, the receptor(s) for Nel has not been identified. Our preliminary studies have already indicated that Nel is a novel axon guidance cue in the visual system. In the proposed research, we will analyze the functions of Nel in development of the visual system and identify its receptor. We expect that the proposed research will reveal the function of Nel in neuronal network formation and the molecular mechanism by which Nel controls behaviour of nerve fibres. In addition, results from this project will have major clinical implications for strategies aimed at neuronal regeneration after brain and spinal cord injuries and for treatment of birth defects affecting the nervous system.

大脑包含一个有序的神经细胞网络，大脑的正确功能严重依赖于神经元网络的正确形成。以人类为例，据估计，大约有10亿个神经细胞形成了超过1万亿个特定的连接。在神经网络的发育过程中，神经纤维必须遵循确定的路径并投射到正确的目标。在这个过程中，神经纤维受到来自其路径和目标的外部分子信号的引导。神经纤维通过特定的“受体”来识别引导信号。因此，研究引导分子与其受体之间的相互作用是阐明脑发育分子机制的关键。这项研究的重点是一种名为Nel的蛋白质。尽管Nel存在于发育中的神经系统中，并且具有在其他发挥重要生物学功能的分子中发现的结构特征，但对其在神经系统发育中的功能知之甚少。此外，Nel的受体尚未确定。我们的初步研究已经表明，Nel在视觉系统中是一种新的轴突引导线索。在本研究中，我们将分析Nel在视觉系统发育中的功能，并鉴定其受体。我们期望所提出的研究将揭示Nel在神经元网络形成中的功能以及Nel控制神经纤维行为的分子机制。此外，该项目的结果将对脑和脊髓损伤后的神经元再生策略以及影响神经系统的出生缺陷的治疗具有重要的临床意义。

项目成果

In vitro guidance of retinal axons by a tectal lamina-specific glycoprotein Nel.

• DOI: 10.1016/j.mcn.2009.02.006
• 发表时间: 2009-06
• 期刊: MOLECULAR AND CELLULAR NEUROSCIENCE
• 影响因子: 3.5
• 作者: Jiang, Yulan;Obama, Hiroya;Kuan, Soh Leh;Nakamura, Ritsuko;Nakamoto, Chizu;Ouyang, Zhufeng;Nakamoto, Masaru
• 通讯作者: Nakamoto, Masaru

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development.

• DOI: 10.1091/mbc.e13-08-0453
• 发表时间: 2014-01
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Nakamoto C;Kuan SL;Findlay AS;Durward E;Ouyang Z;Zakrzewska ED;Endo T;Nakamoto M
• 通讯作者: Nakamoto M

Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma.

• DOI: 10.1111/cas.12649
• 发表时间: 2015-05
• 期刊: Cancer science
• 影响因子: 5.7
• 作者: Nakamura R;Oyama T;Tajiri R;Mizokami A;Namiki M;Nakamoto M;Ooi A
• 通讯作者: Ooi A