Molecular mechanisms of lipid signaling in the developing nervous system

在中枢神经系统的发育过程中，神经元活动驱动突触连接的规范和成熟。神经元成熟和功能接触形成的过程受到许多基因表达的严格控制，这些基因的表达受发育过程中各种信号通路的激活调节。脂肪酸（脂质）是神经元细胞膜的主要成分，并作为信号分子的供应，如前列腺素E2（PGE2）。在神经系统中，PGE 2可以介导神经元可塑性、学习记忆、树突棘增加和疼痛反应等反应。本研究将探讨PGE2信号在神经系统中的分子机制。该研究计划的目标是：（1）了解PGE2信号及其下游效应物在早期神经元发育中的作用，（2）该途径的异常信号如何对细胞功能产生不利影响并导致神经系统的潜在发育缺陷，（3）为PGE2信号通路与神经系统早期模式化所必需的其他关键通路之间的相互作用提供证据。这项研究将进一步加深我们对大脑如何利用各种途径的合作信号进行发育以及这些途径的信号变化如何导致异常结果的认识。

During the development of the central nervous system, neuronal activity drives the specification and maturation of synaptic connections. The process of neuronal maturation and formation of functional contacts is tightly controlled by expression of numerous genes regulated by activation of various signaling pathways across development. Fatty acids (lipids) are major components of neuronal cell membranes and serve as a supply of signaling molecules, such as prostaglandin E2 (PGE2). It has been shown that in the nervous system PGE2 can mediate responses such as neuronal plasticity, learning and memory, increase of dendritic spines and pain response. This study will investigate the molecular mechanisms associated with PGE2 signaling in the nervous system. The goals of the proposed research program are (1) to understand the role of PGE2 signaling and its downstream effectors in early neuronal development, (2) how abnormal signaling of this pathway can adversely interfere with cell function and result in potential developmental defects of the nervous system, and (3) to provide evidence for cross talk between PGE2 signaling pathway and another key pathways essential for early patterning of the nervous system. This study will further our knowledge of how the brain uses cooperative signaling of various pathways for its development and how changes in signaling of these pathways may contribute to abnormal outcomes.