title: The biomechanical properties of an epithelial tissue determine the location of its vasculature.
abstract: An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature. In turn, blood vessels accumulate at the islet periphery. Neither alterations in endothelial cell proliferation, apoptosis, morphology, Vegfa expression and VEGF-A secretion nor 'empty sleeves' of vascular basement membrane are found. Instead, biophysical experiments reveal that the biomechanical properties of pancreatic islet cells, such as their actomyosin-mediated cortex tension and adhesive forces to endothelial cells, are significantly changed. These results suggest that a sorting event is driving the segregation of endothelial and epithelial cells and indicate that the epithelial biomechanical properties determine whether the blood vasculature invades or envelops a growing epithelial tissue.
authors.affiliation: Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225 Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Beta Cell Biology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kragl
authors.affiliation: Eidgenössische Technische Hochschule Zürich, Department of Biosystems Science and Engineering, CH-4058 Basel, Switzerland.
authors.forename: Rajib
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225 Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Beta Cell Biology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Haiko
authors.initials: H
authors.lastname: Karsjens
authors.affiliation: Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Otter
authors.affiliation: Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225 Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Beta Cell Biology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartosinska
authors.affiliation: German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Jeruschke
authors.affiliation: German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weiss
authors.affiliation: German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Paul Langerhans Institute Dresden (PLID) of Helmholtz Center Munich at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, D-85764 Neuherberg, Germany.|DFG-Center for Regenerative Therapies Dresden (CRTD), Faculty of Medicine, Technische Universität Dresden, D-01307 Dresden, Germany.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Eidgenössische Technische Hochschule Zürich, Department of Biosystems Science and Engineering, CH-4058 Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Alsteens
authors.affiliation: German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kuss
authors.affiliation: German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Paul Langerhans Institute Dresden (PLID) of Helmholtz Center Munich at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, D-85764 Neuherberg, Germany.|DFG-Center for Regenerative Therapies Dresden (CRTD), Faculty of Medicine, Technische Universität Dresden, D-01307 Dresden, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Speier
authors.affiliation: Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eberhard
authors.affiliation: Eidgenössische Technische Hochschule Zürich, Department of Biosystems Science and Engineering, CH-4058 Basel, Switzerland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.affiliation: Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225 Düsseldorf, Germany.|German Center for Diabetes Research (DZD e.V.), D-85764 München-Neuherberg, Germany.|Institute for Beta Cell Biology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Lammert
mesh_terms: D000205:Actomyosin / Q000502:physiology; D000818:Animals; D001485:Basement Membrane / Q000502:physiology; D001696:Biomechanical Phenomena; D002448:Cell Adhesion / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D004848:Epithelium / Q000098:blood supply* / Q000502:physiology*; D005260:Female; D018149:Glucose Intolerance / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D000205:Actomyosin; D007328:Insulin; D017346:Protein Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D000099200:Scaffold Protein ILK; C467480:vascular endothelial growth factor A, mouse