Notch4 is essential for the maintenance of vascular homeostasis in the young adult pituitary posterior lobes

Abstract

Abstract Notch signaling is critical for vascular development. However, the functions vary significantly depending on organs and the developmental stage. The adult vasculature is less susceptible to Notch signaling inhibition. Vessels in the adult pituitary posterior lobes maintain characteristics of immature vessels, such as sensitivity to VEGF. Here, we show that Notch4 deficiency caused reduction of vascular density, vascular branch length and the number of branching points and the larger radius vessels in the adult pituitary posterior lobes using the automated vascular image analysis method. Upregulation of NR2F2 by Notch4 loss induced arteriovenous identity deficiency. Notch4 has been reported to have dual roles on the regulation of RBP-J-mediated transcription. DAPT is a γ-secretase inhibitor, which inhibits Notch signaling. DAPT-treated adult pituitary posterior lobes showed similar vascular phenotypes to that of Notch4 knockout mice except for the length of affected larger radius vessels, suggesting the importance of RBP-J-mediated transcription in vascular maintenance of the adult pituitary posterior lobes. These data indicate that the maintenance of adult pituitary posterior lobe vasculature requires Notch signaling.