Tumor metastasis currently presents the greatest obstacle for effective cancer remediation. Metastatic growth necessitates both degradation of a specialized form of extracellular matrix (ECM) known as the basement membrane (BM) and the invasion of surrounding tissues thereafter. The thoracic air sacs of fruit flies (Drosophila melanogaster), which develop and operate in a fashion comparable to the human lung, provide a unique model for identifying and characterizing factors that contribute to its own development as well as tumoral invasion. We investigated the involvement of both Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signaling and a BMassociated protein during the development of air sac primordia (ASPs), the precursors to Drosophila air sacs. We find that JAK/STAT signaling occurs in ASP tip cells and that misexpression of core pathway components via the GAL4/UAS system negatively impacts ASP development. Further, we identify Unpaired 2 (Upd2) as the primary activating ligand for JAK/STAT activity in the ASP. Knockdown of the BM-associated protein using GAL4 drivers associated with a fibroblast growth factor (FGF) receptor gene, breathless (btl), and segment polarity gene, patched (ptc), prevented larval development beyond the second larval instar (L2). Knockdown of the BM-associated protein in the wing also produced bristle defects, but its overexpression did not have an effect anywhere other than in the ASP, where the proportion of mutant phenotypes increased significantly (p < .0001) in response. Finally, we find that collagen IV localization was unaffected by knockdown of the BM-associated protein. Together, our data constitute a significant step forward in understanding the role of both this BM-associated protein and JAK/STAT signaling in the ASP and similar mammalian structures.
| Identifer | oai:union.ndltd.org:WKU/oai:digitalcommons.wku.edu:theses-4093 |
| Date | 01 October 2018 |
| Creators | Powers, Nathan Anthony |
| Publisher | TopSCHOLAR® |
| Source Sets | Western Kentucky University Theses |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Masters Theses & Specialist Projects |
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