Clustered cell migration: Modeling the model system of Drosophila border cells

Abstract In diverse developmental contexts, certain cells must migrate to fulfill their roles. Many questions remain unanswered about the genetic and physical properties that govern cell migration. While the simplest case of a single cell moving alone has been well-studied, additional complexities arise in considering how cohorts of cells move together. Significant differences exist between models of collectively migrating cells. We explore the experimental model of migratory border cell clusters in Drosophila melanogaster egg chambers, which are amenable to direct observation and precise genetic manipulations. This system involves two special characteristics that are worthy of attention: border cell clusters contain a limited number of both migratory and non-migratory cells that require coordination, and they navigate through a heterogeneous three-dimensional microenvironment. First, we review how clusters of motile border cells are specified and guided in their migration by chemical signals and the physical impact of adjacent tissue interactions. In the second part, we examine questions around the 3D structure of the motile cluster and surrounding microenvironment in understanding the limits to cluster size and speed of movement through the egg chamber. Mathematical models have identified sufficient gene regulatory networks for specification, the key forces that capture emergent behaviors observed in vivo, the minimal regulatory topologies for signaling, and the distribution of key signaling cues that direct cell behaviors. This interdisciplinary approach to studying border cells is likely to reveal governing principles that apply to different types of cell migration events.