Notch通道(大多數(shù)多細(xì)胞生物中的一個(gè)普遍存在的細(xì)胞信號(hào)作用體系)是胚胎中的一個(gè)重要調(diào)控因子,,在成年個(gè)體的很多組織中仍然活躍。
現(xiàn)在,,一種采用一個(gè)轉(zhuǎn)基因果蠅庫(它們對(duì)果蠅基因組中幾乎每個(gè)基因都表達(dá)“RAN干涉”(RNAi)構(gòu)造)進(jìn)行的整個(gè)基因組范圍的分析方法,,被用來研究果蠅發(fā)育中的一個(gè)形態(tài)形成事件(該事件是人們最了解的形態(tài)形成事件之一):對(duì)外傳感器官的形成,。利用RNAi篩選方法,被認(rèn)為參與Notch相互作用的基因可以采用一種具有組織特異性的方式使其失去活性,。這樣所獲得的數(shù)據(jù),,使得研究人員有可能將一些假設(shè)存在的功能分配給果蠅基因中大約20%的蛋白編碼基因,并且發(fā)現(xiàn)了參與非對(duì)稱細(xì)胞分裂的6個(gè)新基因及調(diào)控Notch信號(hào)通道的23個(gè)新基因,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.