Purkinje cell arrival at the Purkinje cell layer orchestrates cerebellar foliation and its temporal sequence

Cerebellar foliation proceeds in a stereotyped manner, but the developmental mechanisms that regulate its temporal sequence remain unclear. In reeler and yotari, abnormal Purkinje cell (PC) positioning and foliation defects coexist, yet their causal relationship remains unsolved. Here, using temporally controlled, PC-specific deletion of DAB1, we examined how PC migration relates to foliation. We show that postnatal DAB1 loss disrupts PC positioning and foliation in lobules VI/VII, and that even mild PC displacement from the PC layer (PCL) reduces local proliferation of granule cell precursors (GCPs), while Sonic hedgehog (SHH) supplementation rescues these foliation defects. Furthermore, we find that PC arrival at the PCL differs across lobules, accompanied by lobule-specific peaks in GCP proliferation. These findings identify PC arrival at the PCL as a developmental process that enables effective SHH signaling, thereby promoting foliation, and indicate that spatial differences in PC arrival timing orchestrate the temporal sequence of cerebellar foliation.