Dynamically regulated focal adhesions coordinate endothelial cell remodelling in developing vasculature

Chau, TCY; Keyser, MS; Da Silva, JA; Morris, EK; Yordanov, TE; Duscyz, KP; Paterson, S; Yap, AS; Hogan, BM; Lagendijk, AK

Author(s): Chau, TCY; Keyser, MS; Da Silva, JA; Morris, EK; Yordanov, TE; Duscyz, KP; Paterson, S; Yap, AS; Hogan, BM; Lagendijk, AK;
Details: Publication Year 2022-12-01,Volume 149,Issue #23,Page dev200454
Journal Title: Development
Publication Type: Research article
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.
Keywords: Animals; *Focal Adhesions/metabolism; *Talin/genetics/metabolism; Actins/metabolism; Zebrafish/genetics/metabolism; Endothelial Cells/metabolism; Integrins/genetics/metabolism; Cell Adhesion; Cell-cell junctions; Endothelial cell remodelling; Focal adhesions; Talin1; Vinculin; Zebrafish
Department(s): Laboratory Research
PubMed ID: 36314606
Publisher's Version: https://doi.org/10.1242/dev.200454
Open Access at Publisher's Site: https://doi.org/10.1242/dev.200454
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-16 03:58:14

Last Modified: 2024-10-16 03:59:23