Planar Polarity Is Positively Regulated by Casein Kinase Iɛ in Drosophila

Members of the casein kinase I (CKI) family have been implicated in regulating canonical Wnt/Wingless (Wg) signaling by phosphorylating multiple pathway components [1Knippschild U. Gocht A. Wolff S. Huber N. Lohler J. Stoter M. The casein kinase 1 family: participation in multiple cellular processes in eukaryotes.Cell. Signal. 2005; 17: 675-689Crossref PubMed Scopus (410) Google Scholar, 2Price M.A. CKI, there's more than one: casein kinase I family members in Wnt/Wingless and Hedgehog signaling.Genes Dev. 2006; 20: 399-410Crossref PubMed Scopus (205) Google Scholar]. Overexpression of CKI in vertebrate embryos activates Wg signaling [3Peters J.M. McKay R.M. McKay J.P. Graff J.M. Casein kinase I transduces Wnt signals.Nature. 1999; 401: 345-350Crossref PubMed Scopus (374) Google Scholar, 4Sakanaka C. Leong P. Xu L. Harrison S.D. Williams L.T. Casein kinase I epsilon in the Wnt pathway: regulation of beta-catenin function.Proc. Natl. Acad. Sci. USA. 1999; 96: 12548-12552Crossref PubMed Scopus (187) Google Scholar], and one target is thought to be the cytoplasmic effector Dishevelled (Dsh), which is an in vitro target of CKI phosphorylation. Phosphorylation of Dsh by CKI has also been suggested to switch its activity from noncanonical to canonical Wingless signaling [5Cong F. Schweizer L. Varmus H. Casein kinase I epsilon modulates the signaling specificities of Dishevelled.Mol. Cell. Biol. 2004; 24: 2000-2011Crossref PubMed Scopus (124) Google Scholar]. However, in vivo loss-of-function experiments have failed to identify a clear role for CKI in positive regulation of Wg signaling. By examining hypomorphic mutations of the Drosophila CKIɛ homolog discs overgrown (dco)/double-time, we now show that it is an essential component of the noncanonical/planar cell polarity pathway. Genetic interactions indicate that dco acts positively in planar polarity signaling, demonstrating that it does not act as a switch between canonical and noncanonical pathways. Mutations in dco result in a reduced level of Dishevelled phosphorylation in vivo. Furthermore, in these mutants, Dishevelled fails to adopt its characteristic asymmetric subcellular localisation at the distal end of pupal wing cells, and the site of hair outgrowth is disrupted. Finally, we also find that dco function in polarity is partially redundant with CKIα.