Induction of pancreatic differentiation by signals from blood vessels

Science. 2001 Oct 19;294(5542):564-7. doi: 10.1126/science.1064344. Epub 2001 Sep 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / embryology*
  • Aorta / physiology
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Culture Techniques
  • Embryonic Induction*
  • Endoderm / physiology*
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / embryology
  • Endothelium, Vascular / physiology*
  • Eye Proteins
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Insulin / biosynthesis
  • Insulin / genetics
  • Islets of Langerhans / blood supply
  • Islets of Langerhans / cytology
  • Islets of Langerhans / embryology*
  • Islets of Langerhans / metabolism
  • Lymphokines / biosynthesis
  • Lymphokines / genetics
  • Mesoderm / physiology
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Morphogenesis
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pancreas / blood supply
  • Pancreas / cytology
  • Pancreas / embryology*
  • Repressor Proteins
  • Signal Transduction
  • Stomach / blood supply
  • Stomach / cytology
  • Stomach / embryology
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Xenopus laevis

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Endothelial Growth Factors
  • Eye Proteins
  • Homeodomain Proteins
  • Insulin
  • Lymphokines
  • Nerve Tissue Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins
  • Trans-Activators
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • pancreatic and duodenal homeobox 1 protein
  • Neurogenic differentiation factor 1