Endothelial Notch1 drives multicellular remodelling during hyaloid vessel regression.

Hyaloid vessel regression is essential for vitreous transparency and normal vision, yet how this transient vascular network is dismantled remains unclear. Here we show that postnatal hyaloid regression in mice is not driven by a measurable increase in apoptosis, but instead by coordinated endothelial and mural cell delamination, extravascular redistribution and a transient plasticity program marked by Snail1 and Slug induction. Notch1 signalling peaks during the regression window, and vascular endothelial-specific Notch1 deletion causes persistent hyaloid vessels, with excessive proliferation and failure of endothelial and mural cell disengagement. Mechanistically, loss of Notch1 preserves endothelial identity, suppresses an endothelial-mesenchymal transition-like transcriptional program and reduces expression of the Wnt co-recepteors Lrp5 and Lrp6. Wnt pathway mutant phenocopies the delamination defect, supporting functional convergence between Notch1 and Wnt signalling during vessel involution. Together, these findings identify Notch1 as a key driver of developmental vascular pruning. They also redefine hyaloid regression as an apoptosis-non-exclusive remodelling process, with broader implications for physiological and pathological vascular remodelling, and may guide therapeutic strategies to modulate vascular regression in ocular disorders.