Prrc2a-mediated post-transcriptional modulation shapes microglial function and cerebellar development

The crosstalk between microglia and neurons has been regarded as a crucial process during development. However, this process is largely unknown in cerebellum. The present study probes into the role of Prrc2a, a posttranscriptional regulator, specifically within cerebellar microglia, utilizing a microglia-specific knockout mouse model. Prrc2a emerged as a crucial regulator of microglial function, influencing transcripts pivotal for brain development. Single-cell RNA sequencing underscored transcriptomic shifts in Prrc2a-deleted microglia, revealing an abnormal immune-activate state. Prrc2a deficiency and alteration of cerebellar microglia are associated with reduced mutual interactions, altered Purkinje cell morphology, reduced molecular layer width, and subsequently alteration in neuronal function, and defects in motor balance and coordination. Collectively, this study provides novel insights into the molecular mechanisms governing microglial-neuronal interactions within the cerebellum. To investigate the role of Prrc2a in microglia, we utilized microglia-specific knockout mice and ablated Prrc2a at postnatal day1. In order to gain a more comprehensive understanding of Prrc2a deficiency on microglial transcriptome characteristics and subsequent neuronal changes in cerebellum, we performed single-cell RNA-sequencing of 18658 murine cerebellar cells from Prrc2a cKO (specific deletion of Prrc2a in microglia) and Prrc2a flox/flox (control) mice at postnatal day7.