title: Vascular development in the vertebrate pancreas.
abstract: The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium.
authors: Department of Molecular Biology and Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: D Berfin
authors: DB
authors: Azizoglu
authors: Department of Biology, University of North Carolina, Chapel Hill, NC, USA.
authors: Diana C
authors: DC
authors: Chong
authors: Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany.
authors: Alethia
authors: A
authors: Villasenor
authors: Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Judith
authors: J
authors: Magenheim
authors: Department of Molecular Biology and Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: David M
authors: DM
authors: Barry
authors: Department of Molecular Biology and Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Simon
authors: S
authors: Lee
authors: Program in Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Leilani
authors: L
authors: Marty-Santos
authors: Department of Molecular Biology and Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Stephen
authors: S
authors: Fu
authors: Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Yuval
authors: Y
authors: Dor
authors: Department of Molecular Biology and Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Electronic address: ondine.cleaver@utsouthwestern.edu.
authors: Ondine
authors: O
authors: Cleaver
mesh_terms: D000818:Animals; D001158:Arteries / Q000196:embryology; D001808:Blood Vessels / Q000196:embryology*; D019521:Body Patterning; D002196:Capillaries / Q000196:embryology; D004848:Epithelium / Q000098:blood supply; D005260:Female; D018507:Gene Expression Regulation, Developmental; D021621:Imaging, Three-Dimensional; D051379:Mice; D018919:Neovascularization, Physiologic; D010179:Pancreas / Q000098:blood supply* / Q000196:embryology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066253:Vascular Remodeling; D014680:Veins / Q000196:embryology; D014714:Vertebrates / Q000196:embryology*
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Artery; Blood vessel; Endothelial; Epithelium; Heterogeneity; Pancreas; Plexus; VEGF; Vein