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Dev Biol. 2016 Dec 1;420(1):67-78. doi: 10.1016/j.ydbio.2016.10.009. Epub 2016 Oct 24.

Vascular development in the vertebrate pancreas.

Author information

1
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.
2
Department of Biology, University of North Carolina, Chapel Hill, NC, USA.
3
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim 61231, Germany.
4
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
5
Program in Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
6
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.

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.

KEYWORDS:

Artery; Blood vessel; Endothelial; Epithelium; Heterogeneity; Pancreas; Plexus; VEGF; Vein

PMID:
27789228
PMCID:
PMC5125249
DOI:
10.1016/j.ydbio.2016.10.009
[Indexed for MEDLINE]
Free PMC Article

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