Work

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

Year: 2026

Type: article

Abstract: , 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.

Source: iScience

DOI: 10.1016/j.isci.2026.116664

Authors: Ryosuke Uchi, Takao Honda, Takuto Kasai, Yuki Hirota, Kazunori Nakajima

Institutions: Keio University, University of Occupational and Environmental Health Japan

Language: English

Topic: Neurogenesis and neuroplasticity mechanisms

Subfield: Developmental Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,240