Access Type

Open Access Dissertation

Date of Award

January 2015

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Molecular Biology and Genetics

First Advisor

Russell Finley

Abstract

Cyclin Y is a highly conserved member of the Cyclin superfamily of proteins. In Drosophila the Cyclin Y gene (CycY) is required for progression through several stages of development but the specific pathways that Cyclin Y belongs to and that account for its requirement are not known. Studies in human and Drosophila cell lines have shown that membrane-localized Cyclin Y is required for phosphorylation of the wingless/Wnt co-receptor, arrow/LRP6, and for full activation of the canonical wingless/Wnt pathway. CycY null Drosophila, however, do not phenocopy loss-of-function mutations in canonical wingless pathway genes, suggesting that Cyclin Y may have additional roles outside the wingless pathway in vivo. To identify roles for Cyclin Y in Drosophila I used RNAi to knock down CycY expression in 31 distinct tissue patterns. The screen revealed that expression of the CycY shRNA in specific tissue patterns causes larval lethality and other developmental defects. Knockdown of CycY but not arrow in imaginal discs resulted in bent legs and blistered wings, suggesting defects in the cell adhesion pathway. A transgene expressing a Cyclin Y variant that is not membrane localized suppresses some of the CycY knockdown phenotypes, further suggesting that they are not due to defective Arrow phosphorylation. Genetic and phenotypic evidence suggest that Cyclin Y interacts with the Rho pathway to regulate cell adhesion.

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