The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila
The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila
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DOI：
10.1016/j.cell.2006.03.034
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发表时间：
2006-05-05
期刊：
影响因子：
64.5
通讯作者：
Schmucker, Dietmar
中科院分区：
文献类型：
--
作者：
Chen, Brian E.;Kondo, Masahiro;Schmucker, Dietmar
Dscam的选择性剪接产生了巨大的分子多样性，最多有38，016种不同的受体。目前尚不清楚体内是否需要这种大的多样性。我们研究了Dscam在单个机械感觉神经元的神经元-靶识别中的作用，这些神经元通过多个轴突分支与不同的靶细胞连接。对Dscam空神经元的分析表明，Dscam在轴突分支的生长和定向延伸中起重要作用。表达随机选择的单一异构体不能拯救连接，但恢复基本的轴突延伸和初步分支。此外，产生了两个Dscam等位基因，每个等位基因将最大可能的Dscam多样性减少到22，176种同种型。Dscam多样性的减少导致机械感觉神经元的特定连接缺陷。此外，所观察到的等位基因特异性表型表明异构体之间的功能差异。我们的研究结果提供的证据表明，需要非常大量的结构独特的受体亚型，以确保神经元连接的保真度和精度。
Alternative splicing of Dscam generates an enormous molecular diversity with maximally 38,016 different receptors. Whether this large diversity is required in vivo is currently unclear. We examined the role of Dscam in neuron-target recognition of single mechanosensory neurons, which connect with different target cells through multiple axonal branches' Analysis of Dscam null neurons demonstrated an essential role of Dscam for growth and directed extension of axon branches. Expression of randomly chosen single isoforms could not rescue connectivity but did restore basic axonal extension and rudimentary branching. Moreover, two Dscam alleles were generated that each reduced the maximally possible Dscam diversity to 22,176 isoforms. Reduction of Dscam diversity resulted in specific connectivity defects of mechanosensory neurons. Furthermore, the observed allele-specific phenotypes suggest functional differences among isoforms. Our findings provide evidence that a very large number of structurally unique receptor isoforms is required to ensure fidelity and precision of neuronal connectivity.