Echolocation-like model of directed cell migrationwithin growing tissues

Abstract

During development and regeneration, cells migrate to specific locations within growing tissues. These cells can respond to both biochemical signals and mechanical cues, resulting in directed migration. Such migration is often highly stereotypic. Yet, how cells respond to migratory signals in a robust manner within a growing domain remains an open problem. Here, we propose a model of directed migration in growing tissues motivated by echolocation. The migrating cells generate a signaling gradient that induces a response signal from the moving system boundary. This response signal mediates cellular adhesion to the surrounding matrix and hence modulates the cell migration. We find that such a mechanism can align a series of cells at stable positions within growing systems and can effectively scale to system size. Finally, we discuss the relevance of such a model to fibroblast migration and location within the developing zebrafish caudal fin, which may be regulated by opposing signaling gradients of Slit-Robo pathway components. Significance StatementHow do cells reliably migrate within growing environments? Here, we show that cells can take advantage of an echolocation-like process, whereby they induce a response from the tissue boundary. As they approach the boundary, the response signal strengthens and brings the cell to a fixed position from the boundary. This simple system may be applicable to fibroblast migration in the fin.