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

ABSTRACT: 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.

SUBMITTER: Preau L

PROVIDER: S-EPMC11006894 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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

Préau Laetitia L Lischke Anna A Merkel Melanie M Oegel Neslihan N Weissenbruch Maria M Michael Andria A Park Hongryeol H Gradl Dietmar D Kupatt Christian C le Noble Ferdinand F

Nature communications 20240410 1

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 be ...[more]

PMID: 38600061

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

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

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