title: Multiple endothelial cells constitute the tip of developing blood vessels and polarize to promote lumen formation.
abstract: Blood vessel polarization in the apical-basal axis is important for directed secretion of proteins and lumen formation; yet, when and how polarization occurs in the context of angiogenic sprouting is not well understood. Here, we describe a novel topology for endothelial cells at the tip of angiogenic sprouts in several mammalian vascular beds. Two cells that extend filopodia and have significant overlap in space and time were present at vessel tips, both in vitro and in vivo. The cell overlap is more extensive than predicted for tip cell switching, and it sets up a longitudinal cell-cell border that is a site of apical polarization and lumen formation, presumably via a cord-hollowing mechanism. The extent of cell overlap at the tip is reduced in mice lacking aPKCζ, and this is accompanied by reduced distal extension of both the apical border and patent lumens. Thus, at least two polarized cells occupy the distal tip of blood vessel sprouts, and topology, polarization and lumenization along the longitudinal border of these cells are influenced by aPKCζ.
authors.affiliation: Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Pelton
authors.affiliation: Genetics and Molecular Biology Curriculum, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Wright
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, 0349 Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.affiliation: Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Genetics and Molecular Biology Curriculum, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA bautch@med.unc.edu.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bautch
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000196:embryology*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D011493:Protein Kinase C / Q000378:metabolism*
chemical_list: D011493:Protein Kinase C
keywords: Apical-basal polarity; Blood vessel polarity; Lumen formation; Vessel sprout topology; aPKCζ