Cellular and molecular functions and signalling mechanisms of Nel

大脑包含一个井然有序且千篇一律的神经细胞网络，大脑的正确运作关键取决于神经元网络的正确形成。例如，在人类中，据估计，大约10亿个神经细胞形成了超过1千万亿个特定的连接。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靶点。在这个过程中，神经纤维受到外部分子线索的引导，这些线索来自于它们的路径和目标。引导信号是由神经纤维通过特定的“受体”识别的。因此，研究导向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。这项拟议中的研究重点是一种名为NEL的蛋白质。尽管NEL存在于发育中的神经系统中，并具有在其他发挥重要生物功能的分子中发现的结构特征，但人们对其在神经系统发育中的功能知之甚少。此外，NEL的受体(S)尚未确定。我们的初步研究已经表明，NEL是视觉系统中一种新的轴突引导线索。在拟议的研究中，我们将分析NEL在视觉系统发育中的功能，并确定其受体。我们期望这项拟议的研究将揭示NEL在神经网络形成中的作用，以及NEL控制神经纤维行为的分子机制。此外，该项目的结果将对旨在脑和脊髓损伤后神经元再生的策略以及影响神经系统的出生缺陷的治疗具有重大的临床意义。

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.