title: Dynamic endothelial cell rearrangements drive developmental vessel regression.
abstract: Patterning of functional blood vessel networks is achieved by pruning of superfluous connections. The cellular and molecular principles of vessel regression are poorly understood. Here we show that regression is mediated by dynamic and polarized migration of endothelial cells, representing anastomosis in reverse. Establishing and analyzing the first axial polarity map of all endothelial cells in a remodeling vascular network, we propose that balanced movement of cells maintains the primitive plexus under low shear conditions in a metastable dynamic state. We predict that flow-induced polarized migration of endothelial cells breaks symmetry and leads to stabilization of high flow/shear segments and regression of adjacent low flow/shear segments.
authors.affiliation: Vascular Biology Laboratory, London Research Institute-Cancer Research UK, Lincoln's Inn Laboratories, London, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Franco
authors.affiliation: Vascular Biology Laboratory, London Research Institute-Cancer Research UK, Lincoln's Inn Laboratories, London, United Kingdom.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Jones
authors.affiliation: Centre for Computational Science, Department of Chemistry, University College London, London, United Kingdom; CoMPLEX, University College London, Physics Building, London, United Kingdom; Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, No. 9 Edinburgh Bioquarter, Edinburgh, United Kingdom.
authors.forename: Miguel O
authors.initials: MO
authors.lastname: Bernabeu
authors.affiliation: Vascular Patterning Laboratory, Vesalius Research Center, KU Leuven, Department of Oncology, VIB3, Leuven, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Geudens
authors.affiliation: Vascular Patterning Laboratory, Vesalius Research Center, KU Leuven, Department of Oncology, VIB3, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mathivet
authors.affiliation: Vascular Biology Laboratory, London Research Institute-Cancer Research UK, Lincoln's Inn Laboratories, London, United Kingdom.
authors.forename: Andre
authors.initials: A
authors.lastname: Rosa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Felicia M
authors.initials: FM
authors.lastname: Lopes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Aida P
authors.initials: AP
authors.lastname: Lima
authors.affiliation: Vascular Biology Laboratory, London Research Institute-Cancer Research UK, Lincoln's Inn Laboratories, London, United Kingdom.
authors.forename: Anan
authors.initials: A
authors.lastname: Ragab
authors.affiliation: Vascular Biology Laboratory, London Research Institute-Cancer Research UK, Lincoln's Inn Laboratories, London, United Kingdom.
authors.forename: Russell T
authors.initials: RT
authors.lastname: Collins
authors.affiliation: Vascular Patterning Laboratory, Vesalius Research Center, KU Leuven, Department of Oncology, VIB3, Leuven, Belgium.
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Phng
authors.affiliation: CoMPLEX, University College London, Physics Building, London, United Kingdom.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coveney
authors.affiliation: Vascular Biology Laboratory, London Research Institute-Cancer Research UK, Lincoln's Inn Laboratories, London, United Kingdom; Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, No. 9 Edinburgh Bioquarter, Edinburgh, United Kingdom.
authors.forename: Holger
authors.initials: H
authors.lastname: Gerhardt
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology*; D016764:Cell Polarity; D004730:Endothelium, Vascular / Q000166:cytology*; D008954:Models, Biological