Induction of pancreatic differentiation by signals from blood vessels.
Blood vessels supply developing organs with metabolic sustenance. Here, we demonstrate a role for blood vessels as a source of developmental signals during pancreatic organogenesis. In vitro experiments with embryonic mouse tissues demonstrate that blood vessel endothelium induces insulin expression in isolated endoderm. Removal of the dorsal aorta in Xenopus laevis embryos results in the failure of insulin expression in vivo. Furthermore, using transgenic mice, we show that ectopic vascularization in the posterior foregut leads to ectopic insulin expression and islet hyperplasia. These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development.
Lammert
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Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Cleaver
O
O
Melton
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D
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D046508:Culture Techniques; D004627:Embryonic Induction; D004707:Endoderm / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D005136:Eye Proteins; D005753:Gastric Mucosa / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000098:blood supply / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010179:Pancreas / Q000098:blood supply / Q000166:cytology / Q000196:embryology*; D012097:Repressor Proteins; D015398:Signal Transduction; D013270:Stomach / Q000098:blood supply / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014982:Xenopus laevis
D051792:Basic Helix-Loop-Helix Proteins; D016228:Endothelial Growth Factors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C000605732:Pax6 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1