Genetic and cellular analysis of glial development and function in vertebrates

胶质细胞是具有多种功能的非神经元细胞，其功能范围从形成髓鞘到保护神经元。 大脑抵抗感染我们研究的一个主要目标是利用强大的实验优势， 斑马鱼发现新的基因是必不可少的发展和功能的两类神经胶质细胞， CNS、少突胶质细胞和小胶质细胞。 少突胶质细胞在CNS中的轴突上形成髓鞘。当少突胶质细胞开始使轴突形成髓鞘后， 只有一个很短的发育窗口（或“关键期”）来延长新的髓鞘形成过程。利用遗传 和细胞的方法，我们已经确定了一些积极和消极的监管机构， 髓鞘形成我们的目标之一是确定这些因素如何在发育过程中控制髓鞘形成， 神经可塑性和髓鞘再生此外，我们还将探讨关键期的分子基础。 小神经胶质细胞是CNS中的高度能动的吞噬性神经胶质细胞，其破坏病原体并清除碎片， 凋亡细胞和受损的轴突。尽管小胶质细胞在CNS健康和疾病中的重要性，但许多人认为， 关于这些细胞的关键问题仍有待解决。我们进行了斑马鱼突变筛选 发现必要的小胶质细胞基因，我们正在使用体内成像来表征它们的功能， 其他方法。 从这些研究中获得的机械论见解将促进我们对中枢神经系统的基本理解。 神经系统，阐明了在大脑疾病中被破坏的途径，并提出了途径 用于治疗神经系统疾病

Glia are non-neuronal cells with diverse functions that range from forming the myelin sheath to defending the brain against infection. A major goal of our research is to use the powerful experimental advantages of zebrafish to discover new genes that are essential for the development and function of two classes of glia in the CNS, oligodendrocytes and microglia. Oligodendrocytes form myelin on axons in the CNS. After an oligodendrocyte begins to myelinate axons, it has only a short developmental window (or “critical period”) to extend new myelinating processes. Using genetic and cellular approaches in zebrafish, we have identified a number of positive and negative regulators of myelination. One of our goals is to determine how these factors control myelination during development, neural plasticity, and remyelination. In addition, we will investigate the molecular basis of the critical period. Microglia are highly motile, phagocytic glial cells in the CNS that destroy pathogens and clear debris such as apoptotic cells and damaged axons. Despite the importance of microglia in CNS health and disease, many critical questions remain to be addressed about these cells. We have conducted zebrafish mutational screens to discover essential microglial genes, and we are characterizing their functions using in vivo imaging and other approaches. The mechanistic insight gained from these studies will advance our fundamental understanding of the central nervous system, illuminate the pathways that are disrupted in diseases of the brain, and suggest avenues toward therapies for neurological disorders.