Blood vessels restrain pancreas branching, differentiation and growth

Judith Magenheim, Ohad Ilovich, Alon Lazarus, Agnes Klochendler, Oren Ziv, Roni Werman, Ayat Hija, Ondine Cleaver, Eyal Mishani, Eli Keshet, Yuval Dor

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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 perfusionindependent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.

Original languageEnglish (US)
Pages (from-to)4743-4752
Number of pages10
JournalDevelopment
Volume138
Issue number21
DOIs
StatePublished - Nov 1 2011

Keywords

  • Blood vessels
  • Branching
  • Mouse
  • Organ size
  • Pancreas development
  • VEGF
  • Vascular niche

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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