title: The temporal basis of angiogenesis.
abstract: The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about thetime-basedproperties of angiogenesis, despite timing being central to other areas of biology. Here, we present a novel, time-based formulation of endothelial cell behaviour during angiogenesis and discuss a flurry of our recent, integratedin silico/in vivostudies, put in context to the wider literature, which demonstrate that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated 'temporal regulators' have recently been uncovered, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular decisions to migrate. We will argue that 'temporal adaptation' provides a novel account of organ/disease-specific vascular morphology and reveals 'timing' as a new target for therapeutics. We therefore propose and explain a conceptual shift towards a 'temporal adaptation' perspective in vascular biology, and indeed other areas of biology where timing remains elusive.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.
authors.affiliation: Computational Biology Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA kbentley@bidmc.harvard.edu.|Cellular Adaptive Behaviour Laboratory, Rudbeck Laboratories, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Katie
authors.identifier: http://orcid.org/0000-0002-9391-659X
authors.initials: K
authors.lastname: Bentley
authors.affiliation: Computational Biology Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Chakravartula
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic
keywords: active perception; adaptation; dynamics; morphogenesis; time; vascular