Regulation of wingless signaling by the CKI family in Drosophila limb development

Lei Zhang, Jianhang Jia, Bing Wang, Kazuhito Amanai, Keith A. Wharton, Jin Jiang

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The Wingless (Wg)/Wnt signaling pathway regulates a myriad of developmental processes and its malfunction leads to human disorders including cancer. Recent studies suggest that casein kinase I (CKI) family members play pivotal roles in the Wg/Wnt pathway. However, genetic evidence for the involvement of CKI family members in physiological Wg/Wnt signaling events is lacking. In addition, there are conflicting reports regarding whether a given CKI family member functions as a positive or negative regulator of the pathway. Here we examine the roles of seven CKI family members in Wg signaling during Drosophila limb development. We find that increased CKIε stimulates whereas dominant-negative or a null CKIε mutation inhibits Wg signaling. In contrast, inactivation of CKIα by RNA interference (RNAi) leads to ectopic Wg signaling. Interestingly, hypomorphic CKIε mutations synergize with CKIα RNAi to induce ectopic Wg signaling, revealing a negative role for CKIε. Conversely, CKIα RNAi enhances the loss-of-Wg phenotypes caused by CKIε null mutation, suggesting a positive role for CKIα. While none of the other five CKI isoforms can substitute for CKIα in its inhibitory role in the Wg pathway, several CKI isoforms including CG12147 exhibit a positive role based on overexpression. Moreover, loss of Gilgamesh (Gish)/CKIγ attenuates Wg signaling activity. Finally, we provide evidence that several CKI isoforms including CKIα and Gish/CKIγ can phosphorylate the Wg coreceptor Arrow (Arr), which may account, at least in part, for their positive roles in the Wg pathway.

Original languageEnglish (US)
Pages (from-to)221-237
Number of pages17
JournalDevelopmental Biology
Volume299
Issue number1
DOIs
StatePublished - Nov 1 2006

Keywords

  • CKI
  • Cancer
  • Kinase
  • Limb development
  • Signaling
  • Wg
  • Wnt
  • β_catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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