The focus of the proposed experiments is to investigate cell signaling mechanisms between cell layers during organogenesis. Our previous work has shown that the columnar cells and the peripodial ceils in imaginal discs of Drosophila both grow in precise proportion to each other, suggesting coordinated regulation by a global size control mechanism. The first specific aim of this proposal is to provide a molecular description of the signaling pathways between the two cell layers. Studies with Drosophila imaginal discs are advantageous because upon identification of a pathway, we can remove or activate components of the pathway. This will tell us whether the pathway is only used for size control or organ identity or both. Based on preliminary data we focus our study on the wg, dpp, hh, and insulin signaling pathways between the two cell layers. In Drosophila, just as in other organisms, upon the wounding of an organ, wound healing occurs. A cut through an imaginal disc brings two cell layers together, and the two cell layers fuse shortly afterwards.
The second aim of the proposal examines whether the molecular signals identified in the first specific aim also function in regeneration after wound healing. Preliminary observations indicate that wingless induces fate map changes necessary for regeneration. An understanding of how molecular signaling increases developmental potency during regeneration is key for stem cell biology.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Cell Development and Function Integrated Review Group (CDF)
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Carter, Anthony D
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University of Washington
Schools of Arts and Sciences
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Ing, Thomas; Tseng, Alexander; Sustar, Anne et al. (2013) Sp1 modifies leg-to-wing transdetermination in Drosophila. Dev Biol 373:290-9
Schubiger, Gerold; Schubiger, Margrit; Sustar, Anne (2012) The three leg imaginal discs of Drosophila: ""Vive la difference"". Dev Biol 369:76-90
Sustar, Anne; Bonvin, Marianne; Schubiger, Margrit et al. (2011) Drosophila twin spot clones reveal cell division dynamics in regenerating imaginal discs. Dev Biol 356:576-87
Schubiger, Margrit; Sustar, Anne; Schubiger, Gerold (2010) Regeneration and transdetermination: the role of wingless and its regulation. Dev Biol 347:315-24
Griffin, Ruth; Sustar, Anne; Bonvin, Marianne et al. (2009) The twin spot generator for differential Drosophila lineage analysis. Nat Methods 6:600-2
McClure, Kimberly D; Sustar, Anne; Schubiger, Gerold (2008) Three genes control the timing, the site and the size of blastema formation in Drosophila. Dev Biol 319:68-77
McClure, Kimberly D; Schubiger, Gerold (2008) A screen for genes that function in leg disc regeneration in Drosophila melanogaster. Mech Dev 125:67-80
McClure, Kimberly D; Schubiger, Gerold (2007) Transdetermination: Drosophila imaginal disc cells exhibit stem cell-like potency. Int J Biochem Cell Biol 39:1105-18
Sustar, Anne; Schubiger, Gerold (2005) A transient cell cycle shift in Drosophila imaginal disc cells precedes multipotency. Cell 120:383-93
McClure, Kimberly D; Schubiger, Gerold (2005) Developmental analysis and squamous morphogenesis of the peripodial epithelium in Drosophila imaginal discs. Development 132:5033-42

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