GSE122117
The role of beta-catenin signaling in regulating barrier vs. non-barrier gene expression programs in circumventricular organ and ocular vasculatures
The mammalian brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in the circumventricular organs (CVOs), a set of small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively. We show here that endothelial cells in these vascular systems exhibit a low level of beta-catenin signaling. By elevating beta-catenin signaling in endothelial cells, these vasculatures can be partially converted to a barrier state. In one CVO, the area postrema, high permeability is maintained, in part, by local production of Wnt inhibitory factor-1. Overall design: RNA-seq and ATAC-seq of adult vascular endothelial cells (ECs) from the cerebellum, anterior pituitary, and posterior pituitary of Tie2-GFP mice, with and without beta-catenin stabilization; RiboTag RNA-seq of adult vascular ECs from the cortex and choroid plexus, with and without beta-catenin stabilization. Information about the RiboTag mouse is available at: https://depts.washington.edu/mcklab/RiboTag.html