Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth
Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth
ABSTRACT The development of the retinal vasculature is essential to maintain health of the tissue, but the developmental mechanisms are not completely understood. The aim of this study was to investigate the cell-autonomous role of retinoic acid signaling in endothelial cells during retina vascular development. Using a temporal and cell-specific mouse model to disrupt retinoic acid signaling in endothelial cells in the postnatal retina (Pdgfbicre/+ dnRAR403fl/fl mutants), we discovered that angiogenesis in the retina is significantly decreased with a reduction in retina vascularization, endothelial tip cell number and filipodia, and endothelial ‘crowding’ of stalk cells. Interestingly, by P15, the vasculature can overcome the early angiogenic defect and fully vascularized the retina. At P60, the vasculature is intact with no evidence of retina cell death or altered blood retinal barrier integrity. Further, we identified that the angiogenic defect seen in mutants at P6 correlates with decreased Vegfr3 expression in endothelial cells. Collectively, our work identified a previously unappreciated function for endothelial retinoic acid signaling in early retinal angiogenesis.
Como Christina N.、Pawlikowski Brad、Siegenthaler Julie、Cervantes Cesar
University of Colorado Anschutz Medical Campus, Department of Pediatrics, Section of Developmental Biology||University of Colorado Anschutz Medical Campus, Neuroscience Graduate Program||University of Colorado Anschutz Medical Campus, Summer Research Training ProgramUniversity of Colorado Anschutz Medical Campus, Department of Pediatrics, Section of Developmental BiologyUniversity of Colorado Anschutz Medical Campus, Department of Pediatrics, Section of Developmental Biology||University of Colorado Anschutz Medical Campus, Neuroscience Graduate Program||University of Colorado Anschutz Medical Campus, Summer Research Training ProgramUniversity of Colorado Anschutz Medical Campus, Department of Pediatrics, Section of Developmental Biology||University of Colorado Anschutz Medical Campus, Summer Research Training Program
眼科学基础医学生物科学研究方法、生物科学研究技术
Retinoic acidblood-retinal barrierendothelial cellsCNS angiogenesisVEGFR3
Como Christina N.,Pawlikowski Brad,Siegenthaler Julie,Cervantes Cesar.Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2022.05.09.491241.点此复制
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