Laminin deposition is dispensable for vasculogenesis but regulates blood vessel diameter independent of flow.
Basement membranes (BMs) consisting of laminins, collagens, and heparan sulfate proteoglycans (HSPGs) are vital for proper endothelial cell function, but many aspects of their role in vascular development remain unknown. Here, we demonstrate that vascular structures within differentiating embryoid bodies are wrapped in a BM composed of alpha4- and alpha5-chain laminins, fibronectin, collagen IV, and HSPGs. In sprouting angiogenesis, laminins were produced by stalk cells, as well as the leading tip cell, and deposited along the sprout length, including tip cell filopodia. In embryonic stem cells deficient in laminins, due to lamc1 (laminin gamma1) deletion, vascular development and organization were largely unaffected. However, the frequency of vessels with wide lumens was increased 4-fold. Laminin-deficient vessels were moreover characterized by increased fibronectin levels and enhanced endothelial cell proliferation. We conclude that laminins are dispensable for vascular development but that they regulate lumen formation in the absence of flow and vascular tone.
Jakobsson
Lars
L
Department of Genetics and Pathology, Uppsala University, Dag Hammarskjöldsv 20, SE-75185, Uppsala, Sweden.
Domogatskaya
Anna
A
Tryggvason
Karl
K
Edgar
David
D
Claesson-Welsh
Lena
L
D000818:Animals; D001485:Basement Membrane / Q000196:embryology; D001808:Blood Vessels / Q000033:anatomy & histology / Q000196:embryology*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D007797:Laminin; D042461:Vascular Endothelial Growth Factor A; C089141:laminin gamma 1; C467480:vascular endothelial growth factor A, mouse