Investigating the Role of Wntless isoforms in Wingless Signaling

Lombardi, Nicholas
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University of Delaware
nts are secreted signaling molecules that have essential functions in development and adult homeostasis. This family of proteins as well as the wnt signal transduction pathway is conserved from humans to invertebrates, including Drosophila. Wingless (Wg) is the founding member of the Drosophila Wnt family. Wg secretion forms a morphogen gradient that elicits different signals in its short and long-range targets. Wntless (Wls) is a highly conserved multi-pass transmembrane protein that binds to Wg and escorts it through the secretion pathway. Wls exists in two isoforms within the cell designated Wls-A and Wls-B. The goal of this research was to determine the relative abundance of the two Wls isoforms, and determine the difference in their functions. Quantitative PCR analysis results showed considerably higher levels Wls-B in the Drosophila imaginal wing discs. Since, wls-B is predominate isoform expressed in the wing imaginal disc I explored the phenotypic consequences of overexpressing each isoform in the posterior compartment of the developing wing disc. Overexpression of Wls-A showed a shift of Wg from the apical to basal surface of the wing disc, overexpression of Wls-B showed an overall decrease in Wg expression. After observing phenotypic differences in the wing imaginal disc, I investigated the effects of overexpression on the adult wings. Overexpression of Wls- A in various patterns resulted in visible deformations in adult wings. Conversely, overexpression of Wls-B in the same patterns did not result in any adult phenotypes. Additionally, both phenotypes were capable of rescuing a Wls double mutant to adult viability. Taken together these results suggest that the cellular function of Wls A and B both differ and overlap. The detailed molecular, cellular and developmental consequences of these differences will be examined in future experiments.