PUBLICATION
Dynamically regulated focal adhesions coordinate endothelial cell remodelling in developing vasculature
- 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.
- ID
- ZDB-PUB-221101-11
- Date
- 2022
- Source
- Development (Cambridge, England) 149(23): (Journal)
- Registered Authors
- Da Silva, Jason, Hogan, Ben M., Paterson, Scott, Yap, Alpha
- Keywords
- Cell-cell junctions, Endothelial cell remodelling, Focal Adhesions, Talin1, Vinculin, Zebrafish
- MeSH Terms
-
- Actins/metabolism
- Animals
- Cell Adhesion
- Endothelial Cells/metabolism
- Focal Adhesions*/metabolism
- Integrins/genetics
- Integrins/metabolism
- Talin*/genetics
- Talin*/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 36314606 Full text @ Development
Citation
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. (2022) Dynamically regulated focal adhesions coordinate endothelial cell remodelling in developing vasculature. Development (Cambridge, England). 149(23):.
Abstract
The assembly of a mature vascular network involves coordinated endothelial cell (EC) shape changes, including a process of EC elongation. How EC elongation is dynamically regulated in vivo is not fully understood. Here, we generated a zebrafish mutant, deficient for the integrin adaptor protein Talin1. Using a new Focal Adhesion (FA) marker line, expressing endothelial Vinculinb-eGFP, we demonstrated that EC FAs function dynamically and are lost in our talin1 mutants, allowing us to uncouple the primary roles of FAs in ECs morphogenesis, from the secondary effects that occur due to systemic vessel failure or loss of blood flow. Talin1 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 FA dynamics and EC elongation during vascular morphogenesis. Together, we have identified that FAs are essential for EC elongation and junction linearisation in flow pressured vessels and 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping