Genetic and cellular analysis of glial development and function in vertebrates

胶质细胞是一种非神经细胞，具有多种功能，从形成髓鞘到防御 大脑抗感染。我们研究的一个主要目标是利用微处理器强大的实验优势 斑马鱼将发现对两类胶质细胞的发育和功能至关重要的新基因 中枢神经系统、少突胶质细胞和小胶质细胞。 少突胶质细胞在中枢神经系统的轴突上形成髓鞘。少突胶质细胞开始形成髓鞘轴突后， 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。使用遗传 和斑马鱼的细胞途径，我们已经确定了一些积极和消极的调节因子 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，我们还将研究临界期的分子基础。 小胶质细胞是中枢神经系统中高度能动的、吞噬的胶质细胞，它可以摧毁病原体并清除碎片，如 凋亡的细胞和受损的轴突。尽管小胶质细胞在中枢神经系统健康和疾病中很重要，但许多 有关这些细胞的关键问题仍有待解决。我们已经进行了斑马鱼突变筛查 为了发现必要的小胶质细胞基因，我们正在使用体内成像和 其他方法。 从这些研究中获得的机械洞察力将促进我们对中央的根本理解 神经系统，照亮在大脑疾病中被破坏的路径，并提出途径 神经疾病的治疗方法。

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.