Investigating the role of WNTless (Wls) in wingless (Wg) gradient formation

Basiri, Babak
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University of Delaware
Wingless (Wg), the predominant Drosophila Wnt, is a secreted signaling ligand. Like other Wnts in vertebrates, it is required to execute numerous phases of the Drosophila developmental program. Formation of a morphogen gradient is one strategy used by Wg to drive pattern formation during embryonic development. Wntless (Wls) is a multipass transmembrane protein required for Wingless (Wg) secretion from producing cells and a conserved component of the Wnt signaling pathway. The goal of this research was to determine the role of Wls in Wg signaling and morphogen gradient formation. Observed phenotypes caused by overexpression of Wls in the wing imaginal disc of Drosophila support the hypothesis that wls overexpression will change the shape of the Wg morphogen gradient in the wing disc. In the presence of excessive Wls, more Wg is targeted toward the long-range concentration gradient at the expense of short-range signaling. As a result, long-range targets of Wg signaling would be expressed over a longer distance from the secretion source. Expression of short-range targets of Wg, on the other hand, will be attenuated which is best demonstrated by the lack of wing margin in wls-overexpressing flies. I also showed that endosomal acidification is necessary for proper Wg secretion, and wls-overexpressing cells are more resistant to the effects of acidification inhibition. This observation suggests that there is a functional relationship between Wls and endosomal acidification in Wg intracellular trafficking and secretion. At the end of this writing, I present a model to explain this interrelation.