PUBLICATION
Local Cortical Tension by Myosin II Guides 3D Endothelial Cell Branching
- Authors
- Fischer, R.S., Gardel, M., Ma, X., Adelstein, R.S., and Waterman, C.M.
- ID
- ZDB-PUB-090204-35
- Date
- 2009
- Source
- Current biology : CB 19(3): 260-265 (Journal)
- Registered Authors
- Keywords
- CELLBIO
- MeSH Terms
-
- Animals
- Biomechanical Phenomena
- Cell Movement/physiology*
- Endothelial Cells/cytology*
- Endothelial Cells/metabolism
- Extracellular Matrix/physiology
- Models, Anatomic*
- Morphogenesis/physiology*
- Myosin Type II/metabolism
- Myosin Type II/physiology*
- Neovascularization, Physiologic/physiology*
- Pseudopodia/physiology
- Zebrafish
- PubMed
- 19185493 Full text @ Curr. Biol.
Citation
Fischer, R.S., Gardel, M., Ma, X., Adelstein, R.S., and Waterman, C.M. (2009) Local Cortical Tension by Myosin II Guides 3D Endothelial Cell Branching. Current biology : CB. 19(3):260-265.
Abstract
A key feature of angiogenesis is directional control of endothelial cell (EC) morphogenesis and movement [1]. During angiogenic sprouting, endothelial "tip cells" directionally branch from existing vessels in response to biochemical cues such as VEGF or hypoxia and migrate and invade the surrounding extracellular matrix (ECM) in a process that requires ECM remodeling by matrix metalloproteases (MMPs) [2-4]. Tip EC branching is mediated by directional protrusion of subcellular pseudopodial branches [5, 6]. Here, we seek to understand how EC pseudopodial branching is locally regulated to directionally guide angiogenesis. We develop an in vitro 3D EC model system in which migrating ECs display branched pseudopodia morphodynamics similar to those in living zebrafish. Using this system, we find that ECM stiffness and ROCK-mediated myosin II activity inhibit EC pseudopodial branch initiation. Myosin II is dynamically localized to the EC cortex and is partially released under conditions that promote branching. Local depletion of cortical myosin II precedes branch initiation, and initiation can be induced by local inhibition of myosin II activity. Thus, local downregulation of myosin II cortical contraction allows pseudopodium initiation to mediate EC branching and hence guide directional migration and angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping