Chemotaxis of Drosophila border cells is modulated by tissue geometry through dispersion of chemoattractants

Migratory cells respond to graded concentrations of diffusible chemoattractants <i>in vitro</i>, but how complex tissue geometries <i>in vivo</i> impact chemotaxis is poorly understood. To address this, we studied the Drosophila border cells. Live-imaged border cells varied in their chemotactic migration speeds, which correlated positionally with distinct architectures. We then developed a reduced mathematical model to determine how chemoattractant distribution is affected by tissue architecture. Larger extracellular volumes locally dampened the chemoattractant gradient and, when coupled with an agent-based motion of the cluster, reduced cell speeds. This suggests that chemoattractant levels vary by tissue architectures, informing cell migration behaviors locally, which we tested <i>in vivo.</i> Genetically elevating chemoattractant levels slowed migration in specific architectural regions, while mutants with spacious tissue structure rescued defects from high chemoattractant levels, promoting punctual migration. Our results highlight the interplay between tissue geometry and the local distribution of signaling molecules to orchestrate cell migration.