title: Cdc42 regulates branching in angiogenic sprouting in vitro.
abstract: The morphogenetic events that occur during angiogenic sprouting involve several members of the Rho family of GTPases, including Cdc42. However, the precise roles of Cdc42 in angiogenic sprouting have been difficult to elucidate owing to the lack of models to study these events in vitro. Here, we aim to identify the roles of Cdc42 in branching morphogenesis in angiogenesis.
  
  
  
  Using a 3D biomimetic model of angiogenesis in vitro, where endothelial cells were seeded inside a cylindrical channel within collagen gel and sprouted from the channel in response to a defined biochemical gradient of angiogenic factors, we inhibited Cdc42 activity with a small molecule inhibitor ML141 and examined the effects of Cdc42 on the morphogenetic processes of angiogenic sprouting.
  
  
  
  We find that partial inhibition of Cdc42 had minimal effects on directional migration of endothelial cells, but led to fewer branching events without affecting the length of these branches. We also observed that antagonizing Cdc42 reduced collective migration in favor of single cell migration. Additionally, Cdc42 also regulated the initiation of filopodial extensions in endothelial tip cells.
  
  
  
  Our findings suggest that Cdc42 can affect multiple morphogenetic processes during angiogenic sprouting and ultimately impact the architecture of the vasculature.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Duc-Huy T
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA, USA.
authors.forename: Alec
authors.initials: A
authors.lastname: Wong
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.|Department of Biomedical Engineering, Boston University, Boston, MA, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
authors.forename: Christopher S
authors.identifier: 0000-0003-2445-8449
authors.initials: CS
authors.lastname: Chen
mesh_terms: D032701:Biomimetics; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008955:Models, Cardiovascular; D009024:Morphogenesis; D018919:Neovascularization, Physiologic; D011554:Pseudopodia; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000096926:Benzenesulfonamides
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D020764:cdc42 GTP-Binding Protein; C581055:CID2950007; D000096926:Benzenesulfonamides; C000626589:CDC42 protein, human
keywords: Cdc42; angiogenesis; biomimetic model; branching; filopodia