Cell-type-specific roles of FOXP1 in the excitatory neuronal lineage during early neocortical murine development

• DOI: 10.1016/j.celrep.2025.115384
• Publication Date: 2025-03-05T18:43:55Z
• Authors: Ana Ortiz; Fatma Ayhan; Nitin Khandelwal; Elliot Outland; Miranda Jankovic; Matthew Harper; Genevieve Konopka
• Keywords: Neocortex; Lineage (genetic); Cell type; Cell lineage

Forkhead box protein P1 (FOXP1), a transcription factor enriched in the neocortex, is associated with autism spectrum disorders (ASDs) and FOXP1 syndrome. Emx1Cre/+;Foxp1fl/fl conditional deletion (Foxp1 knockout [cKO]) mouse cortex leads to overall reduced thickness, alterations cortical lamination, changes relative thickness of layers. However, developmental cell-type-specific mechanisms underlying these remained unclear. We find that Foxp1 results accelerated pseudo-age during early neurogenesis, increased cell cycle exit late altered gene expression chromatin accessibility, selective migration deficits subset upper-layer neurons. These data explain postnatal differences observed layers thickness. also highlight genes regulated by their enrichment high-confidence ASD or synaptic genes. Together, underscore network neurodevelopmental-disorder-related may serve as potential modulatory targets for modification relevant ASDs