Characterization of the cellular and molecular mechanisms that mediate glial tiling

功能性和有效的神经系统的发展需要协调的规范，迁移和 胶质细胞的分化。在中枢和外周神经系统（CNS和PNS， 分别），大量的胶质细胞被指定必须迁移和分化成不仅功能性的， 神经胶质细胞，但也协调其发展，使他们占据离散，不重叠的领土， 邻近的胶质细胞。神经胶质间隔或平铺的这种现象可以发生在CNS、PNS或CNS中发现的神经胶质之间。 其中一个细胞位于CNS中，另一个位于PNS中。虽然我们知道 这些平铺事件发生时，我们不知道这些相互作用的分子性质，也不知道它们是否被 都是平铺的胶质细胞此外，局部神经胶质-神经胶质相互作用如何在全局神经胶质平铺中发挥作用尚不清楚。在这 建议，使用斑马鱼作为模式生物，我们将研究细胞和分子机制， 在运动出口点（MEP）过渡区（TZ）和发育中的脊髓中介导髓鞘形成前胶质细胞平铺 线.在本项目的目标1中，我们将使用表达分析、多色、体内、延时 新鉴定的介质的成像、电子显微镜、药理学和遗传操作（CRISPR） 阐明支配MEP TZs髓鞘形成胶质细胞平铺的细胞和分子机制。在目标2中， 将确定我们在Aim 1中描述的相同机制是否也介导少突胶质细胞之间的平铺 在发育中的脊髓中的前体细胞（OPC）。为了更好地了解、诊断和治疗 CNS和PNS的退行性疾病，我们需要了解其细胞和分子机制 介导神经胶质间的相互作用和平铺。斑马鱼提供了一个独特的机会， 操纵细胞群以深入了解神经胶质细胞在正常生理条件下如何相互作用， 如果这些最终导致神经胶质平铺的相互作用在疾病中受到干扰，

Development of a functional and efficient nervous system requires the orchestrated specification, migration and differentiation of glia. During gliogenesis in both the central and peripheral nervous systems (CNS and PNS, respectively), large populations of glia are specified that must migrate and differentiate into not only functional glial cells, but also coordinate their development so that they occupy discrete, non-overlapping territories with neighboring glia. This phenomenon of glial spacing, or tiling, can occur between glia found in the CNS, PNS, or between glial cells where one cell resides in the CNS and the other resides in the PNS. Although we know that these tiling events occur, we don’t know the molecular nature of these interactions or whether they are used by all tiling glia. Additionally, how local glial-glial interactions play a role in global glial tiling is unknown. In this proposal, using zebrafish as a model organism, we will investigate the cellular and molecular mechanisms that mediate pre-myelinating glial tiling at motor exit point (MEP) transition zones (TZ) and in the developing spinal cord. In Aim 1 of this project, we will use a combination of expression analysis, multi-color, in vivo, time-lapse imaging, electron microscopy, pharmacological and genetic manipulation (CRISPR) of newly identified mediators to elucidate the cellular and molecular mechanisms that govern myelinating glial tiling at MEP TZs. In Aim 2, we will determine if the same mechanisms we characterize in Aim 1 also mediate tiling between oligodendrocyte progenitor cells (OPC) in the developing spinal cord. To better understand, diagnose and treat the many degenerative disorders of the CNS and PNS, we need to comprehend the cellular and molecular mechanisms that mediate glial-glial interactions and tiling. Zebrafish provide a unique opportunity to directly observe and manipulate cell populations to gain insight into how glial cells interact under normal physiological conditions, and if those interactions that ultimately result in glial tiling are perturbed in disease.