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Blood vessels restrain pancreas branching, differentiation and growth.

Authors
  • Magenheim, Judith
  • Ilovich, Ohad
  • Lazarus, Alon
  • Klochendler, Agnes
  • Ziv, Oren
  • Werman, Roni
  • Hija, Ayat
  • Cleaver, Ondine
  • Mishani, Eyal
  • Keshet, Eli
  • Dor, Yuval
Type
Published Article
Journal
Development
Publisher
The Company of Biologists
Publication Date
Nov 01, 2011
Volume
138
Issue
21
Pages
4743–4752
Identifiers
DOI: 10.1242/dev.066548
PMID: 21965615
Source
Medline
License
Unknown

Abstract

How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.

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