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Growth-limiting role of endothelial cells in endoderm development.

Journal article
Authors 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
Published in Developmental biology
Volume 352
Issue 2
Pages 267-77
ISSN 1095-564X
Publication year 2011
Published at
Pages 267-77
Language en
Keywords Animals, Cell Differentiation, Cell Proliferation, Embryonic Development, Endoderm, cytology, embryology, metabolism, Endothelial Cells, cytology, metabolism, Gene Expression Regulation, Developmental, Gestational Age, Homeodomain Proteins, metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Morphogenesis, genetics, physiology, Pancreas, blood supply, cytology, embryology, metabolism, RNA, Messenger, genetics, metabolism, Receptors, Lysosphingolipid, deficiency, genetics, Trans-Activators, metabolism
Subject categories Cell and Molecular Biology


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.

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