Molecular mechanisms of lipid signaling in the developing nervous system

在中枢神经系统的发育过程中，神经元的活动驱动突触连接的规范和成熟。神经元的成熟和功能接触的形成过程受到许多基因表达的严格控制，这些基因的表达受到各种信号通路的激活，这些信号通路贯穿发育过程。脂肪酸(脂)是神经细胞膜的主要成分，并提供信号分子，如前列腺素E2(PGE2)。研究表明，在神经系统中，PGE2可以介导神经元的可塑性、学习和记忆、树突棘的增加和疼痛反应。本研究将探讨神经系统中与PGE2信号相关的分子机制。该研究计划的目标是(1)了解PGE2信号及其下游效应因子在早期神经元发育中的作用，(2)该通路的异常信号如何对细胞功能产生不利干扰并导致潜在的神经系统发育缺陷，以及(3)为PGE2信号通路与神经系统早期模式形成所必需的另一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通路的协同信号来促进其发育，以及这些通路信号的变化如何导致异常结果的了解。

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.