title: Growth-limiting role of endothelial cells in endoderm development.
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 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.
authors.affiliation: Stem Cell and Pancreas Developmental Biology, Stem Cell Center, Department of Laboratory Medicine, Lund, Lund University, BMC B10 Klinikgatan 26, SE-221 84 Lund, Sweden.
authors.forename: Fredrik Wolfhagen
authors.initials: FW
authors.lastname: Sand
authors.forename: Andreas
authors.initials: A
authors.lastname: Hörnblad
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Johansson
authors.forename: Christina
authors.initials: C
authors.lastname: Lorén
authors.forename: Josefina
authors.initials: J
authors.lastname: Edsbagge
authors.forename: Anders
authors.initials: A
authors.lastname: Ståhlberg
authors.forename: Judith
authors.initials: J
authors.lastname: Magenheim
authors.forename: Ohad
authors.initials: O
authors.lastname: Ilovich
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.forename: Ulf
authors.initials: U
authors.lastname: Ahlgren
authors.forename: Henrik
authors.initials: H
authors.lastname: Semb
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D047108:Embryonic Development; D004707:Endoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D010179:Pancreas / Q000098:blood supply / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics; D000081025:Sphingosine-1-Phosphate Receptors; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein