Molecular genetic analysis of drosophila disconnected gene during development

果蝇脱节(DISCO)基因编码中枢和外周神经系统发育所需的C2H2型锌指转录因子。DISCO在发育过程中的表达是动态的，提示该基因在多种发育过程中发挥作用。在之前的资助期间，我们研究了迪斯科在腿部和触角发育过程中近端-远端(P-D)轴模式形成中的一个新功能。P-D轴是指昆虫的附肢(或四肢)从离身体最近的部分(近端)到构成附肢的结构的组织方式。在脊椎动物和昆虫中，无末端(Dll)基因代表着这一重要发育过程的主要调节因子。我们的结果表明，DISCO与依赖Dll的腿和触角的发育以及Dll的正确表达有关。Dll结构域中DISCO基因功能的下调调节在表型和分子上模拟Dll突变。此外，在Dll突变背景下，Dll细胞中DISCO的上调部分挽救了突变的表型。我们的结果表明，DISCO和Dll参与了一个自动调节反馈环，其中Dll是Dll所必需的，并且是DISCO启动子活性的充分条件，而DISCO又是正确的Dll转录所必需的。因此，我提出了一个工作假设，即DISCO作为DLL的辅助因子在P-D模式中发挥作用。最有趣的是，我们的结果表明，DISCO可能通过限制腊肠(DAC)的表达而在触角上作为视网膜细胞命运的抑制因子。在这项拨款申请中，我概述了几个实验，旨在继续我们对DISCO在附件发育中的作用及其与DLL依赖的P-D发育的关系的研究。此外，我建议将这些研究扩展到DLL和DISCO功能在视觉原基和眼睛触角成像盘的细胞命运分配中的关系。

The Drosophila disconnected (disco) gene encodes a C2H2 type zinc finger transcription factor required for the development of central and peripheral nervous system.  disco expression during development is dynamic, suggesting a role for this gene in a variety of developmental processes. During the previous funding period we have investigated a novel function for disco in the patterning of Proximal -Distal (P-D) axis during leg and antennal development. The P-D axis refers to the way insect  appendages (or limbs) are organized from the portion closest to the body (proximal) to the structures that make the ti[p of the appendage. In vertebrates as well as insects the Distal-less (Dll) gene represents the master regulator of this important developmental process.Our results implicated disco in Dll-dependent leg and antenna development and in the proper expression of Dll.  Down regulation of disco gene function in Dll domain mimics Dll mutation phenotypically and molecularly. Moreover up regulation of disco in Dll cells in a Dll mutant background partially rescues the mutant phenotype.  Our results demonstrate that disco and Dll participate in an auto regulatory feedback loop where Dll is required and sufficient for disco promoter activity and disco in turn is required for proper Dll transcription. Thus I propose as a working hypothesis that disco carries out its function in P-D patterning as a cofactor of Dll. Most interestingly our results suggest that disco may be required in the antenna as an inhibitor of retinal cell fate by restricting the expression of dachshund (dac).In this grant application I outline several experiments aimed at continuing our investigations of the role of disco in appendage development and its relationship to Dll dependent P-D development. In addition, I propose to extend these studies to the relationship between Dll and disco function in cell fate allocation in the visual primordium and in the eye antennal imaginal disc.