β-Arrestin1 regulates the morphology and dynamics of microglia in zebrafish in vivo.

Microglia are the primary immune cells in the central nervous system. Microglia typically exist in a 'resting' state in the healthy brain, with ramified processes dynamically exploring the surrounding microenvironment. They become 'activated' under pathological conditions with marked changes in morphology. However, the regulation of their morphology dynamics remains poorly understood. Here, using in vivo time-lapse imaging and three-dimensional morphology analysis of microglia in intact zebrafish larvae, we found that β-arrestin1, a multifunctional protein involved in various signal transductions, cell-autonomously regulated the microglial morphology. Knockdown of β-arrestin1 increased the volume size and process number of microglia but reduced the deformation speed in the resting state. Meanwhile, β-arrestin1 down-regulation led to a high frequency of phagocytic behaviour of microglia. These defects were partially rescued by over-expressing human β-arrestin1 in microglia. Our study indicated that microglial dynamics in the resting state can be regulated cell-autonomously by β-arrestin1 signalling.