Faculty, Staff and Student Publications
Publication Date
12-13-2024
Journal
eLife
Abstract
The blood-brain barrier (BBB) controls the movement of molecules into and out of the central nervous system (CNS). Since a functional BBB forms by mouse embryonic day E15.5, we reasoned that gene cohorts expressed in CNS endothelial cells (EC) at E13.5 contribute to BBB formation. In contrast, adult gene signatures reflect BBB maintenance mechanisms. Supporting this hypothesis, transcriptomic analysis revealed distinct cohorts of EC genes involved in BBB formation and maintenance. Here, we demonstrate that epigenetic regulator's histone deacetylase 2 (HDAC2) and polycomb repressive complex 2 (PRC2) control EC gene expression for BBB development and prevent Wnt/β-catenin (Wnt) target genes from being expressed in adult CNS ECs. Low Wnt activity during development modifies BBB genes epigenetically for the formation of functional BBB. As a Class-I HDAC inhibitor induces adult CNS ECs to regain Wnt activity and BBB genetic signatures that support BBB formation, our results inform strategies to promote BBB repair.
Keywords
Blood-Brain Barrier, Animals, Mice, Epigenesis, Genetic, Histone Deacetylase 2, Endothelial Cells, Wnt Signaling Pathway, Polycomb Repressive Complex 2, Gene Expression Profiling, Signal Transduction, Female
DOI
10.7554/eLife.86978
PMID
39670988
PMCID
PMC11643625
PubMedCentral® Posted Date
12-13-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
