TY - JOUR
T1 - Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells
AU - Lum, Lawrence
AU - Yao, Shenqin
AU - Mozer, Brian
AU - Rovescalli, Alessandra
AU - Von Kessler, Doris
AU - Nirenberg, Marshall
AU - Beachy, Philip A.
PY - 2003/3/28
Y1 - 2003/3/28
N2 - 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 1α, 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.
AB - 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 1α, 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.
UR - http://www.scopus.com/inward/record.url?scp=0037470952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037470952&partnerID=8YFLogxK
U2 - 10.1126/science.1081403
DO - 10.1126/science.1081403
M3 - Article
C2 - 12663920
AN - SCOPUS:0037470952
SN - 0036-8075
VL - 299
SP - 2039
EP - 2045
JO - Science
JF - Science
IS - 5615
ER -