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Cdc42 regulates branching in angiogenic sprouting in vitro
Duc-Huy T Nguyen1, Lin Gao2, Alec Wong3
1Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
Microcirculation (New York, N.Y. : 1994)
|April 5, 2017
Summary
Cellular Cdc42 (cell division control protein 42) regulates blood vessel formation by influencing branching and migration patterns. Inhibition affects branching and promotes single-cell over collective migration.
Area of Science:
- Cell Biology
- Vascular Biology
- Biochemistry
Background:
- Angiogenesis, the formation of new blood vessels, is a complex process involving intricate morphogenetic events.
- Rho family GTPases, particularly Cdc42, are implicated in angiogenesis, but their specific roles remain unclear due to limited in vitro models.
Purpose of the Study:
- To investigate the role of Cdc42 in the branching morphogenesis of angiogenesis using a novel 3D biomimetic model.
- To elucidate how Cdc42 activity influences endothelial cell behavior during angiogenic sprouting.
Main Methods:
- Utilized a 3D biomimetic in vitro model of angiogenesis with endothelial cells in a collagen gel.
- Inhibited Cdc42 activity using the small molecule inhibitor ML141 to observe effects on angiogenic sprouting.
Main Results:
- Partial Cdc42 inhibition reduced endothelial cell branching without affecting branch length.
- Cdc42 antagonism shifted migration from collective to single-cell patterns.
- Cdc42 was found to regulate filopodial extensions in endothelial tip cells.
Conclusions:
- Cdc42 plays a multifaceted role in regulating the morphogenetic processes of angiogenic sprouting.
- Modulation of Cdc42 activity impacts vascular architecture during angiogenesis.