EXPLORING GLIAL INVOLVEMENT IN A MOUSE MODEL OF <EM>NR2F1</EM>-RELATED NEURODEVELOPMENTAL DISORDER

The Nr2f1 gene encodes a transcription factor critical for neurodevelopment and neural plasticity, extensively studied for its functions in neural progenitor specification, cortical patterning, and neurogenesis. In contrast, little is known about Nr2f1 expression and function within glial lineages, despite emerging evidence suggesting its involvement in glial fate decisions and brain homeostasis. Pathogenic variants in NR2F1 cause Bosch–Boonstra–Schaaf Optic Atrophy Syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by intellectual disability, visual impairment, hypotonia, and white matter abnormalities, including optic nerve atrophy and corpus callosum thinning. These white matter alterations, together with cognitive and motor deficits observed in patients, suggests that glial dysfunction, particularly involving oligodendrocytes, may contribute to disease pathophysiology. However, the specific contribution of Nr2f1 to oligodendrocyte lineage regulation remains poorly defined. Here, we investigated Nr2f1 expression and function in oligodendrocytes within the adult dentate gyrus (DG), a hippocampal region involved in cognitive functions, using Nr2f1 haploinsufficient mice. Immunofluorescence analyses revealed that Nr2f1 expression within the oligodendrocyte lineage is restricted to oligodendrocyte precursor cells (OPCs) and is downregulated in post-mitotic oligodendrocytes. Adult Nr2f1 heterozygous mice displayed a reduced oligodendrocyte population in the DG, suggesting a novel role for Nr2f1 in early stages of oligodendrocyte lineage progression. These findings extend the role of Nr2f1 beyond neurons and motivate a broader characterization of Nr2f1 expression across glial populations. Ongoing studies will determine whether the oligodendrocyte deficits observed in the DG are shared across other brain regions, including white matter tracts, providing new insights into glial contributions to BBSOAS pathophysiology.