Dynamically regulated focal adhesions coordinate endothelial cell remodelling in developing vasculature
Open accessPublished version of a preprint
Abstract
The assembly of a mature vascular network involves coordinated endothelial cell (EC) shape changes, including the process of EC elongation. How EC elongation is dynamically regulated in vivo is not fully understood. Here, we have generated a zebrafish mutant that is deficient for the integrin adaptor protein Talin 1 (Tln1). Using a new focal adhesion (FA) marker line expressing endothelial Vinculinb-eGFP, we demonstrate that EC FAs function dynamically and are lost in our tln1 mutants, allowing us to uncouple the primary roles of FAs in EC morphogenesis from the secondary effects that occur due to systemic vessel failure or loss of blood flow. Tln1 loss led to compromised F-actin rearrangements, perturbed EC elongation and disrupted cell-cell junction linearisation in vessel remodelling. Finally, chemical induction of actin polymerisation restored actin dynamics and EC elongation during vascular morphogenesis. Together, we identify that FAs are essential for EC elongation and junction linearisation in flow-pressured vessels and that they influence actin polymerisation in cellular morphogenesis. These observations can explain the severely compromised vessel beds and vascular leakage observed in mutant models that lack integrin signalling. This article has an associated ‘The people behind the papers’ interview.
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Cites
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- Authors
- Chau, T. C. Y., Keyser, M. S., Da Silva, J. A., Morris, E. K., Yordanov, T. E., Duscyz, K. P., Paterson, S., Yap, A. S., Hogan, B. M., & Lagendijk, A. K.
- Affiliations
- The University of Queensland (AU)
- Institute for Molecular Bioscience, The University of Queensland 1 Division of Cell and Developmental Biology , , St Lucia, Queensland 4072 , Australia
- The University of Melbourne (AU)
- Corresponding author
- Lagendijk, Anne Karine
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2022-12-01
- Volume
- 149
- Issue
- 23
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC10214536
- OpenAlex
- W4307776780
- Cited by
- 18
- References
- 5
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 2
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Development (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- University of Queensland
- National Health and Medical Research Council (1136592, 2002436, 1155221)
- Australian Research Council (DP200100737)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- focal adhesions, talin-1, integrin signaling, endothelial cell morphogenesis, vascular morphogenesis, actin polymerization, F-actin rearrangement, zebrafish mutants, vinculin, vascular leakage, vascular remodeling
- MeSH terms
- Actins, Animals, Cell Adhesion, Zebrafish, Integrins, Talin, Focal Adhesions, Endothelial Cells
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