ZFIN ID: ZDB-PUB-150115-8
Formin-mediated actin polymerization at endothelial junctions is required for vessel lumen formation and stabilization
Phng, L.K., Gebala, V., Bentley, K., Philippides, A., Wacker, A., Mathivet, T., Sauteur, L., Stanchi, F., Belting, H.G., Affolter, M., Gerhardt, H.
Date: 2015
Source: Developmental Cell   32: 123-32 (Journal)
Registered Authors: Affolter, Markus, Belting, Heinz-Georg Paul (Henry)
Keywords: none
MeSH Terms:
  • Actin Cytoskeleton/metabolism
  • Actins/metabolism*
  • Adherens Junctions/physiology
  • Animals
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/metabolism*
  • Membrane Proteins/antagonists & inhibitors
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Morpholinos/pharmacology
  • Neovascularization, Physiologic*
  • Oligonucleotides, Antisense/pharmacology*
  • Polymerization
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 25584798 Full text @ Dev. Cell
FIGURES
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.
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