Dong Haiyang, Guo Pengjuan, Zhang Jian, Wu Lili, Fu Ying, Li Lei, Zhu Yanda, Du Yiwen, Shi Jilong, Zhang Shixin, Li Guo, Xu Bingbing, Bian Lina, Zhu Xiaohua, You Wendong, Shi Feng, Yang Xiaofeng, Huang Jianhua, Jin Yongfeng
MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, Yuhangtang Road, Hangzhou, Zhejiang ZJ310058, China.
Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, West Wenyi Road, Hangzhou, Zhejiang ZJ310058, China.
Curr Biol. 2022 Jul 11;32(13):2908-2920.e4. doi: 10.1016/j.cub.2022.05.030. Epub 2022 Jun 2.
Alternative splicing of Drosophila Dscam1 into 38,016 isoforms provides neurons with a unique molecular code for self-recognition and self-avoidance. A canonical model suggests that the homophilic binding of identical Dscam1 isoforms on the sister branches of mushroom body (MB) axons supports segregation with high fidelity, even when only a single isoform is expressed. Here, we generated a series of mutant flies with a single exon 4, 6, or 9 variant, encoding 1,584, 396, or 576 potential isoforms, respectively. Surprisingly, most of the mutants in the latter two groups exhibited obvious defects in the growth, branching, and segregation of MB axonal sister branches. This demonstrates that the repertoires of 396 and 576 Dscam1 isoforms were not sufficient for the normal patterning of axonal branches. Moreover, reducing Dscam1 levels largely reversed the defects caused by reduced isoform diversity, suggesting a functional link between Dscam1 expression levels and isoform diversity. Taken together, these results indicate that canonical self-avoidance alone does not explain the function of Dscam1 in MB axonal wiring.
果蝇Dscam1可变剪接产生38016种异构体，为神经元提供了用于自我识别和自我回避的独特分子编码。一个典型模型表明，蘑菇体（MB）轴突姐妹分支上相同Dscam1异构体的同源结合支持高保真分离，即使只表达一种异构体。在这里，我们生成了一系列具有单个外显子4、6或9变体的突变果蝇，分别编码1584、396或576种潜在异构体。令人惊讶的是，后两组中的大多数突变体在MB轴突姐妹分支的生长、分支和分离方面表现出明显缺陷。这表明396和576种Dscam1异构体的组合不足以实现轴突分支的正常模式形成。此外，降低Dscam1水平在很大程度上逆转了由异构体多样性降低引起的缺陷，表明Dscam1表达水平与异构体多样性之间存在功能联系。综上所述，这些结果表明，仅靠典型的自我回避并不能解释Dscam1在MB轴突布线中的功能。
