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Growth-limiting role of endothelial cells in endoderm development.

Author

  • Fredrik Wolfhagen Sand
  • Andreas Hörnblad
  • Jenny Johansson
  • Christina Lorén
  • Josefina Edsbagge
  • Anders Ståhlberg
  • Judith Magenheim
  • Ohad Ilovich
  • Eyal Mishani
  • Yuval Dor
  • Ulf Ahlgren
  • Henrik Semb

Summary, in English

Endoderm development is dependent on inductive signals from different structures in close vicinity, including the notochord, lateral plate mesoderm and endothelial cells. Recently, we demonstrated that a functional vascular system is necessary for proper pancreas development, and that sphingosine-1-phosphate (S1P) exhibits the traits of a blood vessel-derived molecule involved in early pancreas morphogenesis. To examine whether S1P(1)-signaling plays a more general role in endoderm development, S1P(1)-deficient mice were analyzed. S1P(1) ablation results in compromised growth of several foregut-derived organs, including the stomach, dorsal and ventral pancreas and liver. Within the developing pancreas the reduction in organ size was due to deficient proliferation of Pdx1(+) pancreatic progenitors, whereas endocrine cell differentiation was unaffected. Ablation of endothelial cells in vitro did not mimic the S1P(1) phenotype, instead, increased organ size and hyperbranching were observed. Consistent with a negative role for endothelial cells in endoderm organ expansion, excessive vasculature was discovered in S1P(1)-deficient embryos. Altogether, our results show that endothelial cell hyperplasia negatively influences organ development in several foregut-derived organs.

Department/s

Publishing year

2011

Language

English

Pages

267-277

Publication/Series

Developmental Biology

Volume

352

Issue

2

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1095-564X