We use epithelial tissues of Drosophila pupae to explore how cells remain stable in a particular position and how movement is regulated if a cell is displaced from its niche.
The mechanics of cell movement – cytoskeleton and junction remodeling – have been extensively studied in cells in culture but our understanding of how cell movement is regulated in an in vivo setting remains poor. What signals induce a cell to ‘relax’ its adhesion to cell neighbors and initiate cytoskeletal changes that drive it to a specific niche? Conversely, what are the signals that maintain a stable cell niche?
Movement within the plane of the epithelium is crucial during organogenesis and facilitates tissue plasticity during repair. Conversely, deregulated cell movement out of an epithelium enables metastatic spread of malignant cells. Further, many degenerative diseases are characterized by a loss of cell niche and subsequent cell death (for example, focal segmental glomerulosclerosis). It is of fundamental importance to study the molecular mechanisms that orchestrate and regulate these processes.
Our studies focus on the adaptor protein Cindr and its binding partners. Cindr-complexes regulate junction and cytoskeletal stability. How this is done remains unclear. What is the nature of the Cindr-complexes? How are these regulated? How do these complexes exert context-specific regulation of cell behavior?
We address these important questions in the developing Drosophila pupal eye (RIGHT), which is patterned by specific movements of cells, and wing (BELOW), in which cells are usually stable. These tissues provide opportunities to observe normal and abnormal cell movements in situ.
The mammalian orthologs of Cindr – Cd2ap and Cin85 – are important to maintain cell stability and homeostasis. Indeed, Cd2ap plays a vital role in maintaining the mammalian kidney. Cin85 and its protein interactors have been implicated in cancer progression. The role of Cd2ap and Cin85 in junction and cytoskeleton regulation and the related process of endocytosis remains unclear in these contexts.