Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies
Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies
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DOI：
10.1016/j.neuron.2004.07.020
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发表时间：
2004-09-02
期刊：
影响因子：
16.2
通讯作者：
Zipursky, SL
中科院分区：
文献类型：
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作者：
Zhan, XL;Clemens, JC;Zipursky, SL
Dscam是一个免疫球蛋白（IG）超家族成员，在果蝇中调节轴突导向和靶向。选择性剪接可能产生38，016种亚型，其细胞外IG和跨膜结构域不同。我们证明，Dscam介导的发展中的蘑菇体（MB）的轴突的排序。这与Dscam蛋白表达的精确时空模式相关。我们表明，MB神经元表达不同阵列的Dscam亚型和单个MB神经元表达多种亚型。两种不同的Dscam同种型在其胞外结构域不同，作为转基因引入到单个突变细胞中，部分挽救了突变表型。在一组MB神经元中表达Dscam的一种亚型诱导显性表型，而在单个细胞中表达单一亚型则没有。我们建议，不同的胞外结构域的Dscam共享一个共同的功能，并在相邻轴突的表面上表达的异构体的差异影响它们之间的相互作用。
Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the precise spatiotemporal pattern of Dscam protein expression. We demonstrate that MB neurons express different arrays of Dscam isoforms and that single MB neurons express multiple isoforms. Two different Dscam isoforms differing in their extracellular domains introduced as transgenes into single mutant cells partially rescued the mutant phenotype. Expression of one isoform of Dscam in a cohort of MB neurons induced dominant phenotypes, while expression of a single isoform in a single cell did not. We propose that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.