Oligodendrocyte Lineage Cell Mechanisms of Axon Selection for Myelination

项目总结 少突胶质细胞是中枢神经系统中常驻的髓鞘细胞类型。最近的研究表明 不同类型的神经元在轴突上有不同的髓鞘模式和分布。然而，只有 最近有没有关于髓鞘形成的轴突的身份被考虑。因此，它的作用机制 轴突信号和髓鞘形成的选择在很大程度上仍不清楚。我们的实验室和其他实验室已经证明 神经元活动增加髓鞘形成，突触囊泡沿着髓鞘下的轴突释放 这表明少突胶质细胞可能需要能够接收和解释神经递质信号。 单个少突胶质细胞可以形成多达40个不同轴突的髓鞘，形成一种独特的情况，即一个人 细胞可能需要适应来自许多不同神经元的信号。如何才能实现这一目标？少突胶质细胞 表达许多典型的突触后因子，表面上是为了帮助轴突和髓鞘之间的信号传递， 但这些蛋白质在髓鞘细胞中扮演的角色在很大程度上是未知的。使用斑马鱼模型，这项提议 将利用遗传方法和体内成像来解决两个基本概念：是否存在一种模式 这些突触后因子在少突胶质细胞中的表达和/或定位是否符合 包裹轴突的身份；它们在髓鞘形成过程中起什么作用。这将会实现的 在两个目标中：目标1测试哪些突触后因子表达，这些突触后蛋白定位在哪里， 以及它们在什么时候是重要的；以及Aim 2测试这些蛋白质如何发挥促进髓鞘形成的功能，以及如果有 轴突识别与突触后蛋白在髓鞘形成中的定位和功能之间的关系 少突胶质细胞。

PROJECT SUMMARY Oligodendrocytes are the resident myelinating cell type of the central nervous system. Recent work indicates that different classes of neurons have differing patterns and distribution of myelin along their axons. Yet only recently has the identity of the axons been considered with respect to myelination. Thus, the mechanisms of axon signaling and selection for myelination remain largely unknown. Our lab and others have shown that neuronal activity increases myelination and synaptic vesicle release occurs along axons underneath myelin sheaths, suggesting oligodendrocytes may need to be able to receive and interpret neurotransmitter signaling. A single oligodendrocyte can myelinate up to 40 distinct axons, posing a unique situation where an individual cell may need to adapt to signaling from many different neurons. How might this be achieved? Oligodendrocytes express many canonical post-synaptic factors, ostensibly to aid in signaling between the axon and myelin sheath, but the role these proteins play in myelinating cells is largely unknown. Using a zebrafish model, this proposal will utilize genetic approaches and in vivo imaging to address two fundamental concepts: is there a pattern to the expression and/or localization of these post-synaptic factors in oligodendrocytes and does this correspond to wrapped axonal identity; and what function do they serve in the process of myelination. This will be achieved in two aims: Aim 1 tests what post-synaptic factors are expressed, where these post-synaptic proteins localize, and when are they important; and Aim 2 tests how these proteins function to facilitate myelination, and if there is a correlation between axon identity and localization and function of post-synaptic proteins in myelinating oligodendrocytes.