title: Blood vessels restrain pancreas branching, differentiation and growth.
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 perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
authors.affiliation: Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Judith
authors.initials: J
authors.lastname: Magenheim
authors.forename: Ohad
authors.initials: O
authors.lastname: Ilovich
authors.forename: Alon
authors.initials: A
authors.lastname: Lazarus
authors.forename: Agnes
authors.initials: A
authors.lastname: Klochendler
authors.forename: Oren
authors.initials: O
authors.lastname: Ziv
authors.forename: Roni
authors.initials: R
authors.lastname: Werman
authors.forename: Ayat
authors.initials: A
authors.lastname: Hija
authors.forename: Ondine
authors.initials: O
authors.lastname: Cleaver
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000033:anatomy & histology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004848:Epithelium / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000502:physiology*; D010179:Pancreas / Q000033:anatomy & histology* / Q000098:blood supply* / Q000196:embryology* / Q000254:growth & development; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A