Eph-ephrin signaling couples endothelial cell sorting and arterial specification.

Autor: Stewen J; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Kruse K; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany.; Bioinformatics Service Unit, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Godoi-Filip AT; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Zenia; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Jeong HW; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany.; Sequencing Core Facility, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Adams S; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Berkenfeld F; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Stehling M; Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany., Red-Horse K; Department of Biology, Stanford University, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford, CA, USA., Adams RH; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany. ralf.adams@mpi-muenster.mpg.de., Pitulescu ME; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, D-48149, Münster, Germany. mara.pitulescu@mpi-muenster.mpg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 03; Vol. 15 (1), pp. 2539. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1038/s41467-024-46300-0
Abstrakt: Cell segregation allows the compartmentalization of cells with similar fates during morphogenesis, which can be enhanced by cell fate plasticity in response to local molecular and biomechanical cues. Endothelial tip cells in the growing retina, which lead vessel sprouts, give rise to arterial endothelial cells and thereby mediate arterial growth. Here, we have combined cell type-specific and inducible mouse genetics, flow experiments in vitro, single-cell RNA sequencing and biochemistry to show that the balance between ephrin-B2 and its receptor EphB4 is critical for arterial specification, cell sorting and arteriovenous patterning. At the molecular level, elevated ephrin-B2 function after loss of EphB4 enhances signaling responses by the Notch pathway, VEGF and the transcription factor Dach1, which is influenced by endothelial shear stress. Our findings reveal how Eph-ephrin interactions integrate cell segregation and arteriovenous specification in the vasculature, which has potential relevance for human vascular malformations caused by EPHB4 mutations.
(© 2024. The Author(s).)
Databáze: MEDLINE
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