ABS 050: Loss of PDGFRα Signaling Disrupts Newly Formed Oligodendrocyte Populations in Cerebellar White Matter

Dylan Heinstein ¹ , Sophie Jones ¹, Sofia Torre ¹, You "Yoyo" Zhang ¹, Sonia Mayoral ¹

¹ Brown University Carney Institute for Brain Science, Providence, RI

The Van Wickle Journal (2026) Volume 2, ABS050

Introduction: PDGFRα is a key regulator of oligodendrocyte precursor cell (OPC) proliferation, migration, and survival, but its contribution to later stages of oligodendrocyte lineage progression remains incompletely understood. This thesis investigated whether conditional loss of Pdgfrα in oligodendroglial cells alters the abundance of BCAS1-positive newly formed oligodendrocytes (NFOLs) across CNS regions. Using Olig2Cre;Pdgfrα conditional knockout mice and littermate controls, brain tissue from postnatal day 7 and 3-month animals was immunostained for BCAS1 and Olig2, and NFOL densities were quantified in cerebellar white matter, hippocampal molecular layer, corpus callosum, cortex, and striatum. NFOL densities were largely unchanged across most regions in knockout mice relative to controls. In contrast, cerebellar white matter showed a significant reduction in NFOL density at both ages, indicating a persistent and region-selective effect of PDGFRα loss. Preliminary NG2-positive OPC analysis revealed a similar selective decrease in cerebellar white matter, suggesting that reduced NFOL abundance may result, at least in part, from reduction of the upstream precursor pool. Together, these findings support a model in which PDGFRα signaling is particularly important for maintaining proper oligodendroglial lineage output in cerebellar white matter and demonstrate that disruption of early precursor signaling can produce lasting downstream consequences for newly formed oligodendrocyte populations.

Methods: Olig2Cre;Pdgfrα conditional knockout mice and littermate Pdgfrα floxed controls were used to assess the role of PDGFRα signaling in oligodendroglial lineage progression. Brain tissue was collected from postnatal day 7 and 3-month mice, fixed, sectioned, and immunostained for BCAS1 and Olig2 to identify newly formed oligodendrocytes (NFOLs). Immunofluorescent images were acquired using a Zeiss Axio Imager fluorescence microscope with Apotome. BCAS1+/Olig2+ cells with NFOL morphology were quantified in ImageJ across cerebellar white matter, hippocampal molecular layer, corpus callosum, cortex, and striatum. Cell densities were calculated as cells/mm³. Statistical analyses were performed in GraphPad Prism using two-tailed t-tests with Welch’s correction, a two-way ANOVA to assess genotype- and age-dependent effect, and a post hoc power analysis.

Results: Loss of PDGFRα signaling selectively reduced BCAS1+/Olig2+ NFOL density in cerebellar white matter. At P7, PDGFRα cKO mice showed a significant decrease in NFOL density in cerebellar white matter, while hippocampus, corpus callosum, cortex, and striatum remained comparable to controls. At 3 months, pairwise analysis again showed reduced cerebellar white matter NFOL density, though this genotype effect was not retained under two-way ANOVA. Preliminary NG2+ OPC analysis showed a similar cerebellar white matter-specific reduction, suggesting reduced precursor availability.

Discussion: These findings suggest that PDGFRα signaling is especially important for maintaining oligodendroglial lineage output in cerebellar white matter. The parallel reduction in NG2+ OPCs and BCAS1+/Olig2+ NFOLs supports a model in which decreased NFOL density reflects loss of the upstream precursor pool rather than a broad differentiation defect. This regional specificity indicates that PDGFRα dependence varies across CNS environments. Future studies should test whether reduced NFOL abundance leads to decreased mature oligodendrocyte populations, altered MBP expression, or impaired myelination in cerebellar white matter.