Desai C J, Garrity P A, Keshishian H, Zipursky S L, Zinn K
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Development. 1999 Apr;126(7):1527-35. doi: 10.1242/dev.126.7.1527.
The Dock SH2-SH3 domain adapter protein, a homolog of the mammalian Nck oncoprotein, is required for axon guidance and target recognition by photoreceptor axons in Drosophila larvae. Here we show that Dock is widely expressed in neurons and at muscle attachment sites in the embryo, and that this expression pattern has both maternal and zygotic components. In motoneurons, Dock is concentrated in growth cones. Loss of zygotic dock function causes a selective delay in synapse formation by the RP3 motoneuron at the cleft between muscles 7 and 6. These muscles often completely lack innervation in late stage 16 dock mutant embryos. RP3 does form a synapse later in development, however, because muscles 7 and 6 are normally innervated in third-instar mutant larvae. The absence of zygotically expressed Dock also results in subtle defects in a longitudinal axon pathway in the embryonic central nervous system. Concomitant loss of both maternally and zygotically derived Dock dramatically enhances these central nervous system defects, but does not increase the delay in RP3 synaptogenesis. These results indicate that Dock facilitates synapse formation by the RP3 motoneuron and is also required for guidance of some interneuronal axons The involvement of Dock in the conversion of the RP3 growth cone into a presynaptic terminal may reflect a role for Dock-mediated signaling in remodeling of the growth cone's cytoskeleton.
Dock SH2-SH3结构域衔接蛋白是哺乳动物Nck癌蛋白的同源物,果蝇幼虫中感光神经元轴突的轴突导向和靶标识别需要该蛋白。我们在此表明,Dock在胚胎期的神经元和肌肉附着位点广泛表达,且这种表达模式具有母源和合子两个组分。在运动神经元中,Dock集中于生长锥。合子型dock功能缺失导致RP3运动神经元在肌肉7和肌肉6之间的裂隙处形成突触出现选择性延迟。在16期晚期的dock突变胚胎中,这些肌肉常常完全缺乏神经支配。然而,RP3在发育后期确实形成了突触,因为在三龄突变幼虫中,肌肉7和肌肉6通常是有神经支配的。合子型表达的Dock缺失还会导致胚胎中枢神经系统中一条纵向轴突通路出现细微缺陷。母源和合子源Dock同时缺失会显著加剧这些中枢神经系统缺陷,但不会增加RP3突触发生的延迟。这些结果表明,Dock促进RP3运动神经元形成突触,并且也是一些中间神经元轴突导向所必需的。Dock参与将RP3生长锥转变为突触前终末,这可能反映了Dock介导的信号传导在生长锥细胞骨架重塑中的作用。