PT  - JOURNAL ARTICLE
AU  - Laura Maeso-Alonso
AU  - Hugo Alonso-Olivares
AU  - Nicole Martínez-García
AU  - Javier Villoch-Fernández
AU  - Laura Puente-Santamaría
AU  - Natalia Colas-Algora
AU  - Alfonso Fernández-Corona
AU  - María Elena Lorenzo-Marcos
AU  - Benilde Jiménez
AU  - Lars Holmgren
AU  - Margareta Wilhelm
AU  - Jaime Millan
AU  - Luis del Peso
AU  - Lena Claesson-Welsh
AU  - Margarita M. Marques
AU  - Maria C. Marin
TI  - p73 controls cell junction dynamics during sprouting angiogenesis and acts via Angiomotin
AID  - 10.1101/2022.03.03.482832
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.03.482832
4099  - http://biorxiv.org/content/early/2022/03/04/2022.03.03.482832.short
4100  - http://biorxiv.org/content/early/2022/03/04/2022.03.03.482832.full
AB  - Vascular development comprises vasculogenesis, sprouting and non-sprouting angiogenesis and vessel assembly and remodeling. These processes require the coordinated regulation of intercellular junctions to maintain vascular architecture and vessel barrier. Here we demonstrate a key function for p73 transcription factor orchestrating transcriptional programs involved in the regulation of endothelial cell junction morphology during sprouting angiogenesis. TP73 is required for vessel integrity and stability to maintain the endothelial barrier. p73-downregulation leads to hyperpermeability in vitro, while total-p73 or TAp73-specific knockout results in hemorrhages in vivo. We identified AMOT as a p73 direct transcriptional target. Lack of p73 affects expression, localization, and function of Angiomotin. In turn, stabilization of Angiomotin levels in p73-deficent cells can rescue their junctional defects, altogether demonstrating that AMOT is one of p73-downstream mediators during the regulation of endothelial junction dynamics. These results redefine p73 role in angiogenesis by revealing p73 as a vascular architect that regulates endothelial cell junctions, thereby organizing and stabilizing the endothelial barrier.Summary We explore p73 role in vascular morphogenesis and uncover that it orchestrates gene regulation to organize and stabilize the endothelial barrier during sprouting angiogenesis. Mechanistically, TAp73 isoform modulates transcriptional programs involved in vascular architecture including endothelial junction dynamics via AMOT.Competing Interest StatementThe authors have declared no competing interest.