Molecular mechanisms governing maintenance of neural identity

描述（由申请人提供）：精确的细胞身份是必要的，以维持一个连贯的网络通信神经元。在人脑中，神经网络以良好的控制方式构建，然后经过多次迭代的强化和调制，从而形成一个具有成人认知能力的系统。这种改进大部分发生在童年和青春期，在与环境相互作用的背景下。在这个过程中，特定的细胞在网络中建立了独特的身份；它们的作用既取决于由早期发育程序所定义的初始细胞类型，也取决于它们作为一个整体融入神经系统时所发生的修饰。如果一个神经元在适应周围网络发展的过程中不能保持其初始的基本特征，那么它在系统中的作用可能会被破坏。本研究旨在研究神经元在不断变化的环境中维持其身份的关键方面的分子手段。由于对细胞的多个未定义输入可能难以控制，其影响可能难以跟踪，因此本研究利用了一个系统，其中刺激是明确的，并且细胞身份标记易于跟踪。秀丽隐杆线虫的AWC嗅觉神经元检测一组确定的挥发性化学物质，并可以通过一组特定的分子标记来识别。本研究的目的是识别和表征当神经元首次暴露于外部嗅觉刺激时，AWCs分化后负责维持神经身份的分子。具体而言，本研究旨在：(1)确定AWC神经元在分化后保持其身份所必需的核蛋白NSY-7的作用机制；(2)表征nsy-7基因的表达和调控，以便更好地了解其功能；(3)确定nsy-7与AWCs中负责感觉信号转导的分子途径之间的相互作用。对控制神经同一性维持机制的研究可能有助于阐明某些精神疾病（如精神分裂症）的相关因素，这些疾病似乎部分受遗传控制，但在青春期或青春期后才首次表现出来。导致表面上正常的大脑在发育后期无法获得稳定的因素在很大程度上仍未确定，但表面上稳定的大脑偏离正常状态的疾病却很普遍。因此，阐明通常控制这种现象的基因，并将其应用于精神疾病的治疗和预防，将广泛有利于公众健康和社会。

DESCRIPTION (provided by applicant): Precise cellular identities are necessary to maintain a coherent network of communicating neurons. In the human brain, neural networks are constructed in a well-controlled manner and then subjected to multiple iterations of reinforcement and modulation, resulting in a system capable of adult cognition. Much of this refinement takes place during childhood and adolescence, in the context of interactions with the environment. Throughout this process, specific cells establish unique identities within the network; their roles are dependent both on the initial cell type, defined by an early developmental program, and on the modifications that occur as they become integrated into the nervous system as a whole. If a neuron cannot retain its initial, fundamental characteristics as it adapts itself to the network developing around it, its role in the system may be corrupted. This study aims to examine the molecular means by which a neuron maintains crucial aspects of its identity in a changing environment. Because multiple undefined inputs to a cell may be difficult to control and their effects may be difficult to track, this study makes use of a system in which stimuli are well defined, and markers of cell identity are easy to follow. The AWC olfactory neurons in the nematode C. elegans detect a defined set of volatile chemicals and can be identified by a specific set of molecular markers. The goal of this study is to identify and characterize molecules responsible for maintaining neural identity in the AWCs after differentiation, when the neurons are first exposed to external olfactory stimuli. Specifically, this study aims to: (1) determine the mechanism of action of the nuclear protein, NSY-7, which is required for one of the AWC neurons to retain aspects of its identity after differentiation; (2) characterize the expression and regulation of the nsy-7 gene in order to better understand its function, and (3) define interactions between nsy-7 and the molecular pathway responsible for sensory signal transduction in the AWCs. Examination of the mechanisms controlling maintenance of neural identity may serve to illuminate the factors involved in certain psychiatric disorders, such as schizophrenia, that appear to be partially under genetic control but that first manifest themselves at or after adolescence. The factors responsible for the failure of an apparently normal brain to attain stability late in development remain largely unidentified, but disorders in which an seemingly stable brain departs from its normal state are widespread. Elucidation of the genes that normally control this phenomenon, and their application in the treatment and prevention of psychiatric disease, would therefore be broadly beneficial to public health and to the community.