Conditional Deletion of Delayed Myelination During Early Postnatal Brain Development

(forkhead box G1) syndrome is a neurodevelopmental disorder caused by variants in the gene that affect brain structure and function. Individuals affected by syndrome frequently exhibit delayed myelination in neuroimaging studies, which may impair the rapid conduction of nerve impulses. To date, the specific effects of FOXG1 on oligodendrocyte lineage progression and myelination during early postnatal development remain unclear. Here, we investigated the effects of deficiency on myelin development in the mouse brain by conditional deletion of in neural progenitors using mice and tamoxifen induction at postnatal day 0 (P0). We found that deficiency resulted in a transient delay in myelination, evidenced by decreased myelin formation within the first two weeks after birth, but ultimately recovered to the control levels by P30. We also found that deletion prevented the timely attenuation of platelet-derived growth factor receptor alpha (PDGFRα) signaling and reduced the cell cycle exit of oligodendrocyte precursor cells (OPCs), leading to their excessive proliferation and delayed maturation. Additionally, deletion increased the expression of Hes5, a myelin formation inhibitor, as well as Olig2 and Sox10, two promoters of OPC differentiation. Our results reveal the important role of in myelin development and provide new clues for further exploring the pathological mechanisms of syndrome.