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Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype

Formation of organo-typical vascular networks requires cross-talk between differentiating parenchymal cells and developing blood vessels. Here we identify a Vegfa driven venous sprouting process involving parenchymal to vein cross-talk regulating venous endothelial Vegfa signaling strength and subse...

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Main Authors: Préau, Laetitia (Author) , Lischke, Anna (Author) , Merkel, Melanie (Author) , Oegel, Neslihan (Author) , Weissenbruch, Maria (Author) , Michael, Andria (Author) , Park, Hongryeol (Author) , Gradl, Dietmar (Author) , Kupatt, Christian (Author) , Le Noble, Ferdinand (Author)
Format: Article (Journal)
Language:English
Published: 10 April 2024
In: Nature Communications
Year: 2024, Volume: 15, Pages: 1-22
ISSN:2041-1723
DOI:10.1038/s41467-024-47434-x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-024-47434-x
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Author Notes:Laetitia Préau, Anna Lischke, Melanie Merkel, Neslihan Oegel, Maria Weissenbruch, Andria Michael, Hongryeol Park, Dietmar Gradl, Christian Kupatt & Ferdinand le Noble
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Summary:Formation of organo-typical vascular networks requires cross-talk between differentiating parenchymal cells and developing blood vessels. Here we identify a Vegfa driven venous sprouting process involving parenchymal to vein cross-talk regulating venous endothelial Vegfa signaling strength and subsequent formation of a specialized angiogenic cell, prefabricated with an intact lumen and pericyte coverage, termed L-Tip cell. L-Tip cell selection in the venous domain requires genetic interaction between vascular Aplnra and Kdrl in a subset of venous endothelial cells and exposure to parenchymal derived Vegfa and Apelin. Parenchymal Esm1 controls the spatial positioning of venous sprouting by fine-tuning local Vegfa availability. These findings may provide a conceptual framework for understanding how Vegfa generates organo-typical vascular networks based on the selection of competent endothelial cells, induced via spatio-temporal control of endothelial Kdrl signaling strength involving multiple parenchymal derived cues generated in a tissue dependent metabolic context.
Item Description:Gesehen am 04.02.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-47434-x

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