Fascin in brain development and function

项目摘要 肌动蛋白细胞骨架及其动态调控在细胞周期调控中发挥重要作用 神经元的发育和功能。这项拟议的研究旨在调查 筋膜蛋白是一种肌动蛋白捆绑蛋白家族，与大脑发育和功能有关。Fascin1 在哺乳动物的大脑中展示了一个耐人寻味的表达模式：它高度表达 在发育过程中，但在成人大脑中的表达显著减少 在发育过程中，延长的轴突被引导到它们特定的突触目标 关系。轴突的寻径依赖于顶端的活动生长锥体 发育中的轴突，它感知和响应各种细胞外信号，以 在复杂多变的环境中导航。建议的第一部分 这项研究旨在检验一种假说，即一种肌动蛋白细丝捆绑蛋白家族--筋膜蛋白， 轴突发育过程中生长锥丝状足细胞的形成及动态调节 指导。研究部分将利用我们在增长锥体方面的专业知识 研究和使用多方面的方法，包括成像、分子 操作，以及细胞培养和体外脑组织的联合检测。 虽然在成年人的大脑中着迷1的表达大幅减少，但着迷1仍然存在 在成年海马区高表达。我们将检验这一令人兴奋的假设 在苔藓纤维的形成、维持和重塑中起着重要作用 CA3突触连接。使用体内标记和操纵的组合， 成像和电生理学，我们的目标是第一次评估和建立 SENCE1及其肌动蛋白捆绑在脑发育和突触调节中的作用 成人的大脑。鉴于高水平的着迷1与癌细胞有关 转移，拟议中的工作，着迷1不仅将提供重要的洞察 大脑发育和功能的分子机制，也延伸了我们的 关于许多细胞定向运动背后的肌动蛋白机制的知识 生理和病理事件。

Project Summary The actin cytoskeleton and its dynamic regulation play an essential role in neuronal development and function. The proposed study aims to investigate the role of Fascin, a family of actin bundling proteins, in brain development and function. Fascin1 exhibits an intriguing expression profile in mammalian brains: it is highly expressed during development but the expression is substantially decreased in the adult brain During development, elongating axons are guided to their specific targets for synaptic connections. Axon pathfinding depends on the motile growth cone at the tip of developing axons, which senses and responds to a variety of extracellular signals to navigate through a complex and changing environment. The first part of the proposed study aims to test the hypothesis that fascin, a family of actin filament bundling proteins, functions in the formation and dynamic regulation of growth cone filopodia during axon guidance. The part of research will take advantage of our expertise in growth cone research, and employment of a multifaceted approach involving imaging, molecular manipulation, and combined assays in cell cultures and ex vivo brain tissues. While fascin1 expression is substantially reduced in adult brains, fascin1 remains highly expressed in adult hippocampus. We will test the exciting hypothesis that fascin1 plays an important role in the formation, maintenance, and remodeling of mossy fiber- CA3 synaptic connections. Using a combination of an in vivo labeling and manipulation, imaging, and electrophysiology, we aim to evaluate and establish, for the first time, the role of fascin1 and its actin bundling in brain development and synaptic regulation in adult brain. Given that elevated fascin1 levels have been associated with cancer cell metastasis, the proposed work on fascin1 will not only provide significant insights into the molecular mechanisms of brain development and function, but also extend our knowledge concerning the actin mechanisms underlying directed cell movement in many physiological and pathological events.