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Role of Notch in endothelial biology

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Abstract

The Notch signalling pathway is one of the main regulators of endothelial biology. In the last 20 years the critical function of Notch has been uncovered in the context of angiogenesis, participating in tip-stalk specification, arterial-venous differentiation, vessel stabilization, and maturation processes. Importantly, pharmacological compounds targeting distinct members of the Notch signalling pathway have been used in the clinics for cancer therapy. However, the underlying mechanisms that support the variety of outcomes triggered by Notch in apparently opposite contexts such as angiogenesis and vascular homeostasis remain unknown. In recent years, advances in -omics technologies together with mosaic analysis and high molecular, cellular and temporal resolution studies have allowed a better understanding of the mechanisms driven by the Notch signalling pathway in different endothelial contexts. In this review we will focus on the main findings that revisit the role of Notch signalling in vascular biology. We will also discuss potential future directions and technologies that will shed light on the puzzling role of Notch during endothelial growth and homeostasis. Addressing these open questions may allow the improvement and development of therapeutic strategies based on modulation of the Notch signalling pathway.

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Fig. 1
Fig. 2

source and lower Notch activity. Tip cell specification has been shown to be transient and oscillatory. ECs at the leading edge are exposed to varying growth and biophysical factors, which makes them having different abilities to compete for the tip position. This continuous sensing and reaction to the surrounding tissue microenvironment results in a dynamic exchange among tip and stalk cells during angiogenesis.

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Acknowledgments

Work in Rui Benedito laboratory was supported by the Ministerio de Ciencia y Innovación (SAF2017-89299-P) and European Research Council (ERC-2020-COG n° 101001814). Macarena Fernandez-Chacon was supported by a PhD fellowship from Fundación La Caixa (CX_E-2015-01), Irene Garcia-Gonzalez was supported by La Caixa Severo Ochoa (CX-SO-16-1) and Severin Mühleder was funded by the Austrian Science Fund (FWF) project J4358. The CNIC is currently supported by MCIN and the Pro CNIC Foundation.

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  1. Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029, Madrid, Spain

    Macarena Fernández-Chacón, Irene García-González, Severin Mühleder & Rui Benedito

  2. Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Madrid, Spain

    Macarena Fernández-Chacón

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  1. Macarena Fernández-Chacón
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  2. Irene García-González
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  3. Severin Mühleder
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  4. Rui Benedito
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MF-C, SM, IG-G and RB performed literature search and gave critical input. MF-C designed the figures. MF-C and RB wrote most of the manuscript. All authors read and approved the manuscript.

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Correspondence to Rui Benedito.

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Fernández-Chacón, M., García-González, I., Mühleder, S. et al. Role of Notch in endothelial biology. Angiogenesis 24, 237–250 (2021). https://doi.org/10.1007/s10456-021-09793-7

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