Dpp Signaling Directs Cell Motility and Invasiveness during Epithelial Morphogenesis

Report.-- et al.
Tissue remodeling in development and disease [[1] and [2]] involves the coordinated invasion of neighboring territories and/or the replacement of entire cell populations. Cell guidance, cell matching, transitions from passive to migratory epithelia, cell growth and death, and extracellular matrix remodeling all impinge on epithelial spreading. Significantly, the extracellular signals that direct these activities and the specific cellular elements and mechanisms regulated by these signals remain in most cases to be identified. To address these issues, we performed an analysis of histoblasts (Drosophila abdominal epithelial founder cells [[3] and [4]]) on their transition from a dormant state to active migration replacing obsolete larval epidermal cells (LECs). We found that during expansion, Decapentaplegic (Dpp) secreted from surrounding LECs leads to graded pathway activation in cells at the periphery of histoblast nests. Across nests, Dpp activity confers differential cellular behavior and motility by modulating cell-cell contacts, the organization and activity of the cytoskeleton, and histoblast attachment to the substrate. Furthermore, Dpp also prevents the premature death of LECs, allowing the coordination of histoblast expansion to LEC delamination. Dpp signaling activity directing histoblast spreading and invasiveness mimics transforming growth factor-β and bone morphogenetic proteins' role in enhancing the motility and invasiveness of cancer cells, resulting in the promotion of metastasis [[5] and [6]].
We thank the Vienna Drosophila RNAi Center, the Bloomington Stock Center, and the Transgenic RNAi Resource Project at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing fly stocks used in this study. N.N. held a Formación de Profesorado Universitario PhD studentship, C.P.-R. held a “La Caixa” master fellowship, and S.M.-C. is supported by a PhD fellowship from the Fundação para a Ciência e a Tecnologia (Portugal). N.N. would like to thank U. Tepass for his assistance and support. Research in E.M.-B.'s laboratory is funded by grants from the Spanish Ministry of Science and the European Union. Research in M.A.'s laboratory is supported by the Swiss National Science Foundation, Kanton Basel-Stadt, Kanton Basel-Landschaft, and the European Union.