Growth-limiting role of endothelial cells in endoderm development

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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 S1P1-signaling plays a more general role in endoderm development, S1P1-deficient mice were analyzed. S1P1 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 S1P1 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 S1P1-deficient embryos. Altogether, our results show that endothelial cell hyperplasia negatively influences organ development in several foregut-derived organs.

Original languageAmerican English
Pages (from-to)267-277
Number of pages11
JournalDevelopmental Biology
Volume352
Issue number2
DOIs
StatePublished - 15 Apr 2011

Bibliographical note

Funding Information:
We thank Dr. R. Proia for providing the S1P 1 deficient mouse line and for valuable comments on the manuscript, Dr. K. Gaengel and Dr. C. Betsholtz for constructive discussions and for sharing unpublished data, Dr. C. Wright and BCBC for providing antibodies, Dr. I. Artner for valuable comments on the manuscript, M. Magnusson and C. Ekenstierna for mouse breeding. This work was supported by the Swedish Research Council , Stem Cell Center , Lund University , Swedish Foundation for Strategic Research , NIH Beta Cell Biology Consortium , Juvenile Diabetes Research Foundation , and in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases , The Kempe Foundations , The Swedish Medical Research Council and Umeå University Biotech Grants.

Keywords

  • Blood vessel
  • Endoderm
  • Mesenchyme
  • Morphogenesis
  • Pancreas
  • Sphingosine-1-phosphate 1 receptor

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