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Cell migration is critical throughout a multicellular organism’s life from embryogenesis to immune response and tissue repair and can even go aberrantly wrong in diseases like metastatic cancer. In vitro, graded concentrations of diffusible chemoattractants can guide migrating cells, but less is known about chemoattractant distribution and chemotaxis within living organisms, which have complex tissue geometries. Using the border cells, which migrate collectively in the Drosophila egg chamber during oogenesis, we studied how tissue structure affects chemotaxis in vivo. Live-imaged border cells exhibited variations in their chemotactic migration, which correlated positionally within distinct tissue architectures, specifically acellular gaps at cell-cell intersections. To determine how different regions in the egg chamber’s geometry affect chemical cues, we developed a partial differential equation (PDE) model of chemoattractant distribution within a relevant in silico domain. Using a hybrid mathematical model that couples the chemoattractant PDE and an agent-based motion of the cluster, we found that larger extracellular volumes within intersections could locally dampen chemoattractant gradient magnitudes and slow cluster speed in simulations. In vivo, in response to genetically increasing the levels of a chemoattractant, PDGF- and VEGF-related factor 1, border cells exhibited delayed migration and behaved differently within specific architectural regions, consistent with results in silico. We next altered the architectural regions in the migration domain in half pint (hfp) mutant egg chambers and observed migration behaviors that still correlated with tissue features. Importantly, the abnormal tissue geometry was sufficient to rescue defects due to high levels of chemoattractant and resulted in punctual border cell migration indicating chemoattractant distribution can depend on tissue structure. Our modeling data indicate that chemoattractants are more concentrated in certain tissue architectures and dispersed in other regions, likely informing cell migration speeds and favoring clustered cell movements in tissue that contain varied architectures in vivo. Our results shed light on the intricate interplay between tissue geometry and the local distribution of important signaling molecules in orchestrating the essential process of cell migration.