Dynamic endothelial ephrin-B2 and EphB4 expression characterizes hyaloid vessel regression

Abstract

Arteriovenous endothelial identity coordinates vascular growth and patterning, but whether it is remodeled during developmental vessel regression remains unknown. The mouse hyaloid vasculature is a transient ocular network considered predominantly arterial; its timely regression is required for normal vision, yet the identity of its regressing endothelium has remained largely unexplored. Here, we show that postnatal regression is accompanied by a shift from ephrin-B2-enriched to EphB4-enriched endothelium. Residual ephrin-B2-positive endothelial cells increasingly displayed cleaved caspase-3 labeling, whereas Ki67 positivity increased among EphB4-positive cells. Endothelial-specific Notch1 deletion, which causes persistent hyaloid vessels, accentuated this ephrin-B2-low/EphB4-high profile while reducing apoptotic labeling within residual ephrin-B2-positive cells and increasing proliferation within the EphB4-positive population. Mosaic recombination further showed that recombined endothelial cells preferentially expressed EphB4, whereas neighboring unrecombined cells more frequently retained ephrin-B2, supporting a cell-autonomous contribution of Notch1. Thus, arteriovenous-associated endothelial features remain dynamic during developmental vessel regression, linking endothelial identity to the cellular behaviors accompanying hyaloid remodeling.