PUBLICATION
Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling
- Authors
- Hiepen, C., Benamar, M., Barrasa-Fano, J., Condor, M., Ilhan, M., Münch, J., Hastar, N., Kerkhoff, Y., Harms, G.S., Mielke, T., Koenig, B., Block, S., Rocks, O., Abdelilah-Seyfried, S., Van Oosterwyck, H., Knaus, P.
- ID
- ZDB-PUB-250109-212
- Date
- 2025
- Source
- Communications biology 8: 2121 (Journal)
- Registered Authors
- Abdelilah-Seyfried, Salim
- Keywords
- none
- MeSH Terms
-
- Humans
- Biomechanical Phenomena
- Pseudopodia*/metabolism
- Pseudopodia*/physiology
- Neovascularization, Physiologic*
- Signal Transduction*
- Endothelial Cells/metabolism
- Endothelial Cells/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Cell Movement
- Animals
- Bone Morphogenetic Protein Receptors, Type II*/genetics
- Bone Morphogenetic Protein Receptors, Type II*/metabolism
- cdc42 GTP-Binding Protein/genetics
- cdc42 GTP-Binding Protein/metabolism
- Human Umbilical Vein Endothelial Cells/metabolism
- Zebrafish*/genetics
- PubMed
- 39779836 Full text @ Commun Biol
Citation
Hiepen, C., Benamar, M., Barrasa-Fano, J., Condor, M., Ilhan, M., Münch, J., Hastar, N., Kerkhoff, Y., Harms, G.S., Mielke, T., Koenig, B., Block, S., Rocks, O., Abdelilah-Seyfried, S., Van Oosterwyck, H., Knaus, P. (2025) Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling. Communications biology. 8:2121.
Abstract
Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs). Targeting of Bmpr2 reduced sprouting angiogenesis in zebrafish and BMPR2-deficient human ECs formed fewer filopodia, affecting cell migration and actomyosin localization. Spheroid assays revealed a reduced sprouting of BMPR2-deficient ECs in fibrin gels. Even more strikingly, in mosaic spheroids, BMPR2-deficient ECs failed to acquire tip-cell positions. Yet, 3D traction force microscopy revealed that these distinct cell behaviors of BMPR2-deficient tip cells cannot be explained by differences in force-induced matrix deformations, even though these cells adopted distinct cone-shaped morphologies. Notably, BMPR2 positively regulates local CDC42 activity at the plasma membrane to promote filopodia formation. Our findings reveal that BMPR2 functions as a nexus integrating biochemical and biomechanical processes crucial for TCs during angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping