Wadsworth W G, Bhatt H, Hedgecock E M
Department of Pathology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Neuron. 1996 Jan;16(1):35-46. doi: 10.1016/s0896-6273(00)80021-5.
Netrins are laminin-related proteins that guide circumferential migrations on the ectoderm. To understand how netrin cues direct cell movements, we examined the expression of nematode netrin UNC-6 from embryo to adult. UNC-6 is expressed in 12 types of neuroglia and neurons, creating a hierarchy of netrin cues in the developing nervous system. Comparing gene expression pattern with in vivo phenotypes, we suggest how multiple netrin cues, each with a characteristic role, guide cells and axons during development. We also present the molecular analysis of selective loss-of-function and null alleles. The results indicate that the biological activities of netrins are mediated through distinct protein domains. Subtle mutations in domain VI can produce selective defects in both direction- and tissue-specific guidance. EGF-like module V-2 is essential for dorsal guidance activity; we infer this module is important for interactions between UNC-6 and the dorsal guidance receptor UNC-5.
网蛋白是与层粘连蛋白相关的蛋白质，可引导在外胚层上的周向迁移。为了解网蛋白信号如何指导细胞运动，我们研究了线虫网蛋白UNC-6从胚胎到成虫阶段的表达情况。UNC-6在12种神经胶质细胞和神经元中表达，在发育中的神经系统中形成了一个网蛋白信号层次结构。通过将基因表达模式与体内表型进行比较，我们提出了多种具有独特作用的网蛋白信号在发育过程中如何引导细胞和轴突的。我们还展示了功能选择性丧失和无效等位基因的分子分析。结果表明，网蛋白的生物学活性是通过不同的蛋白质结构域介导的。结构域VI中的微小突变可在方向和组织特异性引导方面产生选择性缺陷。表皮生长因子样模块V-2对背侧引导活性至关重要；我们推断该模块对于UNC-6与背侧引导受体UNC-5之间的相互作用很重要。
