Formin-mediated actin polymerization at endothelial junctions is required for vessel lumen formation and stabilization

Phng, Li-Kun, Gebala, Véronique, Bentley, Katie, Philippides, Andrew, Wacker, Andrin, Mathivet, Thomas, Sauteur, Loïc, Stanchi, Fabio, Belting, Heinz-Georg, Affolter, Markus and Gerhardt, Holger (2015) Formin-mediated actin polymerization at endothelial junctions is required for vessel lumen formation and stabilization. Developmental Cell, 32 (1). pp. 123-132. ISSN 1534-5807

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Abstract

During blood vessel formation, endothelial cells (ECs) establish cell-cell junctions and rearrange to form multicellular tubes. Here, we show that during lumen formation, the actin nucleator and elongation factor, formin-like 3 (fmnl3), localizes to EC junctions, where filamentous actin (F-actin) cables assemble. Fluorescent actin reporters and fluorescence recovery after photobleaching experiments in zebrafish embryos identified a pool of dynamic F-actin with high turnover at EC junctions in vessels. Knockdown of fmnl3 expression, chemical inhibition of formin function, and expression of dominant-negative fmnl3 revealed that formin activity maintains a stable F-actin content at EC junctions by continual polymerization of F-actin cables. Reduced actin polymerization leads to destabilized endothelial junctions and consequently to failure in blood vessel lumenization and lumen instability. Our findings highlight the importance of formin activity in blood vessel morphogenesis.

Item Type: Article
Schools and Departments: School of Engineering and Informatics > Informatics
Depositing User: Andy Philippides
Date Deposited: 19 Jun 2015 14:37
Last Modified: 19 Jun 2015 14:37
URI: http://sro.sussex.ac.uk/id/eprint/54616
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