Wnt/Wingless signaling, Earthbound, and Erect Wing are required for late stages of indirect flight muscle development. Hassina Benchabane, Ai Tian, Yashi Ahmed. Department of Genetics, Geisel School of Medicine at Dartmouth.

   The Wnt/Wingless signaling pathway directs fundamental processes during development, and is required for homeostasis of adult tissues and maintenance of stem cells. Hence, the activity of the Wnt pathway and the transcription of its downstream target genes must be tightly regulated to ensure proper development and to prevent human disease. Because the majority of Wnt responses are context-specific, mechanisms have to be in place to restrict signaling and the activation of target genes to specific tissues and developmental stages. In a forward genetic screen in Drosophila, we recently identified two novel tissue-specific cofactors of the Wnt pathway, Earthbound1 (Ebd1) and Erect Wing (Ewg), which promote Wnt signaling in myoblasts and muscles, and are required for proper development of indirect flight muscles (IFMs). Inactivation of ebd1 or ewg, or disruption of Wnt signaling in muscle cells, leads to a loss of IFMs in adults. We further investigated the role of Ewg, Ebd, and Wnt signaling in muscle development. We find that in ebd1 and ewg mutants, as well as in mutants with disrupted Wnt signaling, IFMs are formed correctly initially, but degenerate during pupation. We show evidence that programmed cell death is involved in this degeneration. These findings indicate that Ewg, Ebd1 and Wnt signaling are required for later stages of IFM development.