title: A screen for X-linked mutations affecting Drosophila photoreceptor differentiation identifies Casein kinase 1α as an essential negative regulator of wingless signaling.
abstract: The Wnt and Hedgehog signaling pathways are essential for normal development and are misregulated in cancer. The casein kinase family of serine/threonine kinases regulates both pathways at multiple levels. However, it has been difficult to determine whether individual members of this family have distinct functions in vivo, due to their overlapping substrate specificities. In Drosophila melanogaster, photoreceptor differentiation is induced by Hedgehog and inhibited by Wingless, providing a sensitive system in which to identify regulators of each pathway. We used a mosaic genetic screen in the Drosophila eye to identify mutations in genes on the X chromosome required for signal transduction. We recovered mutations affecting the transcriptional regulator CREB binding protein, the small GTPase dynamin, the cytoskeletal regulator Actin-related protein 2, and the protein kinase Casein kinase 1α. Consistent with its reported function in the β-Catenin degradation complex, Casein Kinase 1α mutant cells accumulate β-Catenin and ectopically induce Wingless target genes. In contrast to previous studies based on RNA interference, we could not detect any effect of the same Casein Kinase 1α mutation on Hedgehog signaling. We thus propose that Casein kinase 1α is essential to allow β-Catenin degradation and prevent inappropriate Wingless signaling, but its effects on the Hedgehog pathway are redundant with other Casein kinase 1 family members.
authors.affiliation: Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Legent
authors.forename: Josefa
authors.initials: J
authors.lastname: Steinhauer
authors.forename: Magali
authors.initials: M
authors.lastname: Richard
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Treisman
mesh_terms: D051377:Actin-Related Protein 2 / Q000235:genetics; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D048128:Casein Kinase Ialpha / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D050172:Genes, X-Linked; D053823:Hedgehog Proteins / Q000378:metabolism; D008297:Male; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: D051377:Actin-Related Protein 2; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D016271:Proto-Oncogene Proteins c-myc; D051880:Receptors, Notch; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; D050882:CREB-Binding Protein; D066246:ErbB Receptors; D048128:Casein Kinase Ialpha; D034281:Dynamins
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