Microglial Prrc2a regulates microglia-neuron interaction in cerebellum and motor functions in mice

The crosstalk between microglia and neuron has been recognized as a crucial process in the development and disorders of the central nervous system. The present study probes into the role of Prrc2a—a post-transcriptional regulator that binds and stabilizes transcripts pivotal for microglial development—specifically within cerebellar microglia using a microglia-targeted conditional knockout model, identifying it as a crucial regulator of microglial function. Single-cell RNA sequencing underscored a transcriptomic shift in Prrc2a-ablated microglia, revealing an abnormally activated state. Prrc2a deficiency and the consequent alteration of cerebellar microglia were associated with reduced mutual interactions, altered Purkinje cell morphology and electrophysiological activity, decreased molecular layer width, and subsequently defects in motor balance and coordination. Collectively, this study provides insights into the molecular mechanisms underlying microglia-neuron interaction within the cerebellum.