Molecular control of endothelial tube formation from single and aggregated cells by lumen signalling complexes that contain MT1-MMP and CDC42 in 3D collagen matrices

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The first blood vessels to form in the embryo are generated by vasculogenesis. New insight into vasculogenesis in mammals is emerging from studies of various transgenic mice or the use of in vitro systems. The Davis lab for many years now has established the use of unique in vitro models that have the ability of elucidating the molecular controls underlying this vascular event. (Davis, 1996, Davis, 2002, Davis, 2003, Kamei et al, 2006) Prior work has revealed a critical role for extracellular matrices and matrix metalloproteinases as well as RhoGTPases in the molecular control of vascular morphogenesis in three-dimensional (3D) tissue environments. Formation of intracellular vacuoles has also been implicated to be a major mechanism regulating EC lumen development both in vivo and in vitro (Davis et al, 2002, Folkman, 1980, Montesamo, 1988, Nicosia et al, 1982) Even though there is considerable work done in identifying key regulators of EC vasculogenesis there are still many unanswered questions in regards to lumen formation from single cells or from aggregated cells. The experiments described in this dissertation were designed to identify new molecular requirements and further our understanding of EC single and aggregated cell lumen formation in 3D collagen type I matrices.