PBX3 Promotes Oligodendrocyte Progenitor Cell Proliferation and Differentiation During Early Postnatal Development

Pre-B-cell leukemia transcription factor 3 (PBX3) is a TALE homeodomain protein involved in neural development, but its function in oligodendrocyte (OL) differentiation has remained unexplored. Here, we show that PBX3 expression is dynamically regulated during OL lineage progression, with peak expression in the corpus callosum at P14, corresponding to the onset of active myelination. In cultured primary oligodendrocyte precursor cells (OPCs), PBX3 expression peaked at OL-1DIV, an early stage of in vitro differentiation. Using OL lineage-specific Pbx3 conditional knockout mice, we found that Pbx3 deletion reduced the density of SOX10+ OL lineage cells and CC1+ mature OLs in the corpus callosum at P14 and P27, accompanied by decreased MBP expression. Notably, these deficits were largely resolved by P50, indicating an age-dependent rather than absolute requirement for PBX3. EdU labeling revealed reduced OPC proliferation in Pbx3 cKO mice, though the Olig1-Cre driver used for conditional deletion is active in early neural progenitors, and thus contributions from reduced OPC specification or generation cannot be excluded. Consistently, siRNA-mediated Pbx3 knockdown in primary OPCs impaired differentiation and reduced MBP expression in vitro. Collectively, our findings identify PBX3 as a positive regulator of OL differentiation during early postnatal development, with a temporally restricted requirement, and provide insights into the transcriptional control of CNS myelination.