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

ABSTRACT: The transcriptional mechanisms coordinating angiogenic sprouting with the acquisition of barrier properties in the developing central nervous system (CNS) remain incompletely defined. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE332948 | GEO | 2026/06/01

REPOSITORIES: GEO

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Project description:Transcription factor Foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells ; Background and Aims: The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1. Methods: We used a combination of genetic, histochemical, ultrastructural and molecular analysis to study gastric cell lineages with respect to FOXQ1. Results: Within the developing and adult gastrointestinal tract, Foxq1 mRNA is restricted to the stomach, expressed prominently in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface, and required for their complete differentiation. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the predominant stomach mucin, MUC5AC. These observations correspond to a paucity of foveolar-cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells. Conclusions: Taken together, these observations imply that promotion of gastric MUC5AC synthesis is a primary, cell-autonomous function of FOXQ1. This study is the first to implicate a transcription factor in terminal differentiation of foveolar cells and begins to define the requirements to assemble highly specialized organelles and cells in the gastric mucosa. DOI: 10.1053/j.gastro.2008.04.019 Experiment Overall Design: RNA from stomach antrum from 2 of each Satin, Beige, and BL6 mice were compared using microarray analysis.

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

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