Endothelial FOXQ1 is required for CNS angiogenesis and blood brain barrier formation

Here, we demonstrate that the forkhead box transcription factor Foxq1 is essential for CNS angiogenesis and blood-brain barrier (BBB) formation. Endothelial-specific deletion of Foxq1 in mice resulted in defective angiogenesis in the brain and retina, characterized by impaired tip cell identity, reduced vascular coverage, and diminished proliferation.

Moreover, mutant embryos exhibited compromised BBB integrity, evidenced by enhanced leakage of molecular tracers. Single-cell transcriptomics revealed that Foxq1 is enriched in tip cells and barrier-competent capillary populations, and its loss disrupts the transcriptional programs governing both endothelial sprouting and barrier maturation. Mechanistically, Foxq1 couples angiogenic morphogenesis with BBB acquisition by regulating tip cell-enriched transcripts such as Esm1, alongside core barrier determinants including Cdh5 and Mfsd2a.These findings establish Foxq1 as a critical transcriptional link between CNS vascular growth and functional barrier establishment, with implications for understanding neurovascular developmental disorders.