Zheng Hong, Coudiere Ludivine, Camia Cheryl, Colavita Antonio, Culotti Joseph G, Merz David C
Department of Medical and Molecular Genetics, Faculty of Medicine, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Dev Biol. 2007 Oct 1;310(1):44-53. doi: 10.1016/j.ydbio.2007.07.014. Epub 2007 Jul 24.
In C. elegans, ectopic expression of the UNC-5 netrin receptor is sufficient to cause repulsion of growth cones and cells away from ventral sources of the UNC-6/netrin guidance cue. A genetic suppressor screen identified the seu-1 gene as required for repulsion of touch neuron growth cones ectopically expressing unc-5. We report here that seu-1 mutations also enhance the frequency of distal tip cell migrations of unc-5 or unc-40 mutants. The seu-1 gene encodes two novel proteins (SEU-1A and SEU-1B) containing a charged central domain and several regions of low amino acid complexity. Transgenic rescue experiments indicate that seu-1 can act cell autonomously in the touch neurons and distal tip cells and that SEU-1 function requires both the SEU-1A and SEU-1B isoforms. A GFP fusion construct was expressed in a dynamic pattern throughout development and localized in the nuclei of neuronal and non-neuronal cells, including gonadal leader cells. These results implicate nuclear SEU-1 in the interpretation of UNC-6/netrin directional information by migrating growth cones and cells.
在秀丽隐杆线虫中，UNC-5 网蛋白受体的异位表达足以导致生长锥和细胞从 UNC-6/网蛋白引导信号的腹侧来源处排斥开来。一项遗传抑制子筛选鉴定出 seu-1 基因是异位表达 unc-5 的触觉神经元生长锥排斥所必需的。我们在此报告，seu-1 突变还会增加 unc-5 或 unc-40 突变体的远端末梢细胞迁移频率。seu-1 基因编码两种新型蛋白质（SEU-1A 和 SEU-1B），它们含有一个带电荷的中央结构域和几个低氨基酸复杂性区域。转基因拯救实验表明，seu-1 可以在触觉神经元和远端末梢细胞中自主发挥作用，并且 SEU-1 的功能需要 SEU-1A 和 SEU-1B 两种异构体。一种 GFP 融合构建体在整个发育过程中以动态模式表达，并定位于神经元和非神经元细胞的细胞核中，包括性腺引导细胞。这些结果表明核 SEU-1 在迁移的生长锥和细胞对 UNC-6/网蛋白方向信息的解读中发挥作用。
