Notch通道(大多数多细胞生物中的一个普遍存在的细胞信号作用体系)是胚胎中的一个重要调控因子,在成年个体的很多组织中仍然活跃。
现在,一种采用一个转基因果蝇库(它们对果蝇基因组中几乎每个基因都表达“RAN干涉”(RNAi)构造)进行的整个基因组范围的分析方法,被用来研究果蝇发育中的一个形态形成事件(该事件是人们最了解的形态形成事件之一):对外传感器官的形成。利用RNAi筛选方法,被认为参与Notch相互作用的基因可以采用一种具有组织特异性的方式使其失去活性。这样所获得的数据,使得研究人员有可能将一些假设存在的功能分配给果蝇基因中大约20%的蛋白编码基因,并且发现了参与非对称细胞分裂的6个新基因及调控Notch信号通道的23个新基因。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 458, 987-992 (23 April 2009) | doi:10.1038/nature07936
Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi
Jennifer L. Mummery-Widmer1,4, Masakazu Yamazaki1,4,5, Thomas Stoeger1, Maria Novatchkova1,2, Sheetal Bhalerao1,2, Doris Chen3, Georg Dietzl2, Barry J. Dickson2 & Juergen A. Knoblich1
1 Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr-Gasse 3,
2 Research Institute of Molecular Pathology (IMP), Dr Bohr-Gasse 7, and,
3 Max F. Perutz Laboratories (MFPL), Department of Biochemistry, Dr Bohr-Gasse 9, A-1030 Vienna, Austria
4 These authors contributed equally to this work.
5 Present address: The Global COE program, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Genome-wide RNA interference (RNAi) screens have identified near-complete sets of genes involved in cellular processes. However, this methodology has not yet been used to study complex developmental processes in a tissue-specific manner. Here we report the use of a library of Drosophila strains expressing inducible hairpin RNAi constructs to study the Notch signalling pathway during external sensory organ development. We assigned putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes. Using secondary assays, we identified 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway. By integrating our phenotypic results with protein interaction data, we constructed a genome-wide, functionally validated interaction network governing Notch signalling and asymmetric cell division. We used clustering algorithms to identify nuclear import pathways and the COP9 signallosome as Notch regulators. Our results show that complex developmental processes can be analysed on a genome-wide level and provide a unique resource for functional annotation of the Drosophila genome.