Molecular Basis for Endothelial Lumen Formation and Tubulogenesis During Vasculogenesis and Angiogenic Sprouting

George E. Davis, Amber N. Stratman, Anastasia Sacharidou, Wonshill Koh

Research output: Chapter in Book/Report/Conference proceedingChapter

146 Scopus citations


Many studies reveal a fundamental role for extracellular matrix-mediated signaling through integrins and Rho GTPases as well as matrix metalloproteinases (MMPs) in the molecular control of vascular tube morphogenesis in three-dimensional (3D) tissue environments. Recent work has defined an endothelial cell (EC) lumen signaling complex of proteins that controls these vascular morphogenic events. These findings reveal a signaling interdependence between Cdc42 and MT1-MMP to control the 3D matrix-specific process of EC tubulogenesis. The EC tube formation process results in the creation of a network of proteolytically generated vascular guidance tunnels in 3D matrices that are utilized to remodel EC-lined tubes through EC motility and could facilitate processes such as flow-induced remodeling and arteriovenous EC sorting and differentiation. Within vascular guidance tunnels, key dynamic interactions occur between ECs and pericytes to affect vessel remodeling, diameter, and vascular basement membrane matrix assembly, a fundamental process necessary for endothelial tube maturation and stabilization. Thus, the EC lumen and tube formation mechanism coordinates the concomitant establishment of a network of vascular tubes within tunnel spaces to allow for flow responsiveness, EC-mural cell interactions, and vascular extracellular matrix assembly to control the development of the functional microcirculation.

Original languageEnglish (US)
Title of host publicationInternational Review of Cell and Molecular Biology
PublisherElsevier Inc.
Number of pages65
StatePublished - 2011
Externally publishedYes

Publication series

NameInternational Review of Cell and Molecular Biology
ISSN (Print)1937-6448


  • Cdc42
  • Collagen
  • Endothelial lumen formation
  • Extracellular matrix
  • Integrins
  • MT1-MMP
  • Pericytes
  • Rho GTPases
  • Tubulogenesis
  • Vascular basement membrane matrix assembly
  • Vascular guidance tunnels

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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