Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells

被引:413
作者
Lum, L
Yao, SQ
Mozer, B
Rovescalli, A
Von Kessler, D
Nirenberg, M
Beachy, PA [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[2] NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1126/science.1081403
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Classical genetic screens can be limited by the selectivity of mutational targeting, the complexities of anatomically based phenotypic analysis, or difficulties in subsequent gene identification. Focusing on signaling response to the secreted morphogen Hedgehog (Hh), we used RNA interference (RNAi) and a quantitative cultured cell assay to systematically screen functional roles of all kinases and phosphatases, and subsequently 43% of predicted Drosophila genes. Two gene products reported to function in Wingless (Wg) signaling were identified as Hh pathway components: a cell surface protein (Daily-like protein) required for Hh signal reception, and casein kinase 1alpha, a candidate tumor suppressor that regulates basal activities of both Hh and Wg pathways. This type of cultured cell-based functional genomics approach may be useful in the systematic analysis of other biological processes.
引用
收藏
页码:2039 / 2045
页数:7
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