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Laminin deposition is dispensable for vasculogenesis but regulates blood vessel diameter independent of flow

Lars Jakobsson^*, Anna Domogatskaya, Karl Tryggvason, David Edgar and Lena Claesson-Welsh^*,1

^* Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden;

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; and

Department of Human Anatomy, University of Liverpool, Liverpool, UK

¹Correspondence: Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Dag Hammarskjöldsv 20, SE-75185, Uppsala, Sweden. E-mail: lena.welsh{at}genpat.uu.se

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 4- and 5-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 1) 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, L., Domogatskaya, A., Tryggvason, K., Edgar, D., Claesson-Welsh, L. Laminin deposition is dispensable for vasculogenesis but regulates blood vessel diameter independent of flow.

Key Words: angiogenesis • sprouting • basement membrane • VEGF

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