Biology subjects

OUBAHA, M.

Publications and source records attributed to OUBAHA, M..

3 recordsLinked to original sources

bioRxiv2026

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

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.

cell biology↗

bioRxiv2026

Developmental senescence orchestrates hyaloid vessel regression in the postnatal eye

The mammalian eye develops in concert with coordinated growth and remodeling of three vascular networks: the hyaloid vasculature, the choroid and retinal plexus. While retinal and choroidal systems support visual function in the mature eye, the hyaloid network plays a vital yet temporary role supporting the developing lens and inner retina. Regression of the hyaloid network is essential for optical clarity, yet the mechanisms guiding the process remain incompletely understood. Using single-cell RNA sequencing, we show that postnatal mouse hyaloid cells are broadly senescent. Hyaloid vascular smooth muscle, endothelial and immune cells display cell-cycle arrest marked by Cdkn1a with the expression of SASP factors. Genetic ablation of Cdkn1a impedes normal hyaloid regression, demonstrating that developmental senescence is essential for vascular remodeling and functions alongside apoptosis and macrophage-mediated clearance. These findings identify an unrecognized senescence-driven mechanism orchestrating hyaloid involution during ocular development, broadening the understanding of vascular remodeling in the eye.

cell biology↗

bioRxiv2025

Notch1 induces endothelial plasticity to mediate hyaloid vessel involution

Hyaloid vascular regression is a critical developmental process essential for vitreous transparency and normal vision, yet the molecular cues orchestrating its involution remain incompletely defined. Here, we identify Notch1 as a pivotal regulator of hyaloid vessel clearance, acting independently of apoptosis to coordinate endothelial detachment, transient plasticity, and migration. Using an endothelial-specific Notch1 knockout mouse model, we demonstrate that loss of Notch1 results in persistent hyaloid vasculature characterized by excessive proliferation and stabilization of the vascular network. Mechanistically, Notch1 activation during the regression window induces endothelial-to-mesenchymal transition (EndoMT) marked by Snail1 and Slug upregulation. This transcriptional signature is accompanied by detachment of endothelial cells from the vascular tubes. In contrast, Notch1-deficient hyaloid vessels retain endothelial cells stably adherent to the vessel wall. Further analysis reveals that Wnt receptors FZD4, LRP5 and LRP6 previously implicated in hyaloid involution are transcriptionally downregulated in Notch1-deficient hyaloids, suggesting that the collaboration between these processes may occur through crosstalk between the Notch and Wnt pathways. Collectively, our findings uncover a Notch1-driven multicellular regression program that governs developmental vessel regression, redefining the molecular principles of vascular pruning. These results have broad implications for understanding vascular remodeling in both physiological and pathological contexts and may guide therapeutic strategies to modulate vascular regression in ocular disorders. One-Sentence SummaryNotch1 drives hyaloid regression through a multicellular program that defines an apoptosis-non-exclusive paradigm of vessel pruning.

cell biology↗