In Drosophila, the insulin/insulin-like growth factor signalling (IIS) pathway plays a key role in coupling nutritional cues with cell growth and proliferation, and thus is important for coordinating development. Now, using border cells in the Drosophila ovary as a model, two studies reveal a crucial role for IIS in regulating collective cell migration.

In the first study, Stephane Noselli and colleagues report that border cell migration is defective in mutants for the Drosophila insulin receptor (InR). Specifically, they show that dInR is required in outer cells of the border cell cluster for correct migration. The authors also observe that the formation and dynamics of cell protrusions on border cells are perturbed following IIS inhibition. Following on from this, they reveal that IIS regulates the expression of the Drosophila profilin gene chickadee, which in turn controls the formation of F-actin protrusions that are essential for cluster delamination and migration. Finally, they demonstrate that the transcription factor FoxO represses chickadee expression but that the InR-mediated inhibition of FoxO expression at the onset of migration is essential to relieve this repression and thereby promote protrusion formation and border cell migration.

In the second study, Mohit Prasad and co-workers similarly show that border cell migration is inhibited following the down-regulation of InR function and also in mutants for the insulin receptor substrate Chico. Using time-lapse imaging, they demonstrate that the detachment of border cell clusters from surrounding follicle cells is delayed following InR depletion. Their detailed characterisation of border cell dynamics indicates that the protrusions formed in InR-depleted clusters are misdirected, suggesting that InR is required for polarizing the migrating cluster. To investigate this further, the researchers assess the function of the cell polarity protein PAR-1 and report that InR genetically interacts with par-1 and with Spaghetti squash, which encodes a regulatory subunit of Drosophila Myosin, leading the authors to propose that IIS influences PAR-1 activity to control border cell detachment and movement, acting via Myosin.

Together these findings uncover a novel role for IIS in regulating collective cell migration, a finding that has important implications for understanding how IIS influences other developmental, as well as pathological, processes.