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 journalArticle

64 Citations (Scopus)

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

Fingerprint

Blood Vessels
Pancreas
Growth
Endocrine Cells
Organ Size
Acinar Cells
Morphogenesis
Cell Size
Vascular Endothelial Growth Factor A
Epithelium
Endothelial Cells
Epithelial Cells
Phenotype
Liver

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Magenheim, J., Ilovich, O., Lazarus, A., Klochendler, A., Ziv, O., Werman, R., ... Dor, Y. (2011). Blood vessels restrain pancreas branching, differentiation and growth. Development, 138(21), 4743-4752. https://doi.org/10.1242/dev.066548

Blood vessels restrain pancreas branching, differentiation and growth. / Magenheim, Judith; Ilovich, Ohad; Lazarus, Alon; Klochendler, Agnes; Ziv, Oren; Werman, Roni; Hija, Ayat; Cleaver, Ondine; Mishani, Eyal; Keshet, Eli; Dor, Yuval.

In: Development, Vol. 138, No. 21, 01.11.2011, p. 4743-4752.

Research output: Contribution to journalArticle

Magenheim, J, Ilovich, O, Lazarus, A, Klochendler, A, Ziv, O, Werman, R, Hija, A, Cleaver, O, Mishani, E, Keshet, E & Dor, Y 2011, 'Blood vessels restrain pancreas branching, differentiation and growth', Development, vol. 138, no. 21, pp. 4743-4752. https://doi.org/10.1242/dev.066548
Magenheim J, Ilovich O, Lazarus A, Klochendler A, Ziv O, Werman R et al. Blood vessels restrain pancreas branching, differentiation and growth. Development. 2011 Nov 1;138(21):4743-4752. https://doi.org/10.1242/dev.066548
Magenheim, Judith ; Ilovich, Ohad ; Lazarus, Alon ; Klochendler, Agnes ; Ziv, Oren ; Werman, Roni ; Hija, Ayat ; Cleaver, Ondine ; Mishani, Eyal ; Keshet, Eli ; Dor, Yuval. / Blood vessels restrain pancreas branching, differentiation and growth. In: Development. 2011 ; Vol. 138, No. 21. pp. 4743-4752.
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