Biological Sciences, Smith College, Northampton, Massachusetts 01063, USA.
Dev Dyn. 2010 Oct;239(10):2603-18. doi: 10.1002/dvdy.22393.
The formation of the central nervous system depends on the coordinated development of neural and glial cell types that arise from a common precursor. Using an existing group of zebrafish mutants generated by viral insertion, we performed a "shelf-screen" to identify genes necessary for astroglial development and axon scaffold formation. We screened 274 of 315 viral insertion lines using antibodies that label axons (anti-Acetylated Tubulin) and astroglia (anti-Gfap) and identified 25 mutants with defects in gliogenesis, glial patterning, neurogenesis, and axon guidance. We also identified a novel class of mutants affecting radial glial cell numbers. Defects in astroglial patterning were always associated with axon defects, supporting an important role for axon-glial interactions during axon scaffold development. The genes disrupted in these viral lines have all been identified, providing a powerful new resource for the study of axon guidance, glio- and neurogenesis, and neuron-glial interactions during development of the vertebrate CNS.
中枢神经系统的形成依赖于神经和神经胶质细胞类型的协调发育,这些细胞类型来源于共同的前体。我们利用现有的一组通过病毒插入产生的斑马鱼突变体,进行了“架子筛选”,以鉴定对神经胶质发育和轴突支架形成所必需的基因。我们使用标记轴突的抗体(抗乙酰化微管蛋白)和神经胶质(抗 Gfap)对 315 个病毒插入系中的 274 个进行了筛选,并鉴定出 25 个在神经胶质发生、神经胶质模式形成、神经发生和轴突导向方面存在缺陷的突变体。我们还鉴定出了一类影响放射状神经胶质细胞数量的新型突变体。神经胶质模式形成缺陷总是与轴突缺陷相关,这支持了在轴突支架发育过程中轴突-神经胶质相互作用的重要作用。这些病毒系中破坏的基因已全部被鉴定出来,为研究脊椎动物中枢神经系统发育过程中的轴突导向、神经胶质和神经发生以及神经元-神经胶质相互作用提供了一个强大的新资源。