A large-scale functional approach to uncover human genes and pathways in Drosophila  

作　　者：Rong Xu Kejing Deng Yi Zhu Yue Wu Jing Ren Min Wan Shouyuan Zhao Xiaohui Wu Min Han Yuan Zhuang Tian Xu 

机构地区：[1]Institute of Developmental Biology and Molecular Medicine and School of Life Science, Fudan University, Shanghai 200433,China [2]Howard Hughes Medical Institute and Department of MCDB, University of Colorado, Boulder, CO 80309-0347, USA [3]Department of lmmunology, Duke University Medical Center, Durham, NC 27708, USA [4]Howard Hughes Medical Institute and Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, BCMM236, New Haven, CT 06536, USA

出　　处：《Cell Research》2008年第11期1114-1127,共14页细胞研究（英文版）

基　　金：We are grateful to Xizhi Ma, Junnian Zhou, Tianhong Xu, Xu Liu, Xu Ding, Yang Liu, Ying Peng, Congwu Chi, Yiying Shang, Mingyao Ying, Sheng Ding, Lei Sun, Lei Tian, Huanhu Zhu, Hua Huang, Hongmei Li, and Xiaomo Wu for cDNA constructs and partial transgenic work, and Lihui Zhou （East China University of Science and Technology, China） for scanning electron microscopy. We thank Duc Nguyen （Yale University, USA） for critical reading and editing of this manuscript. This work is supported by grants from the National Natural Science Foundation of China （Grant Nos. 30030080, 39970408 and 30470840）, National Basic Research Program of China （973） （Grant No. 2006CB806700）.

摘　　要：We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo.

关 键 词：DROSOPHILA human gene GAL4/UAS genetic screen RPL8 insulin signaling 

分 类 号：Q2[生物学—细胞生物学]