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PMID: 11577200 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Induction of pancreatic differentiation by signals from blood vessels.

Science (New York, N.Y.) ·Vol. 294 ·No. 5542 ·2001-10-19 ·Pages 564-7

Lammert E, Cleaver O, Melton D

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.

MeSH Terms

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

Chemicals

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

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Lammert E

Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.

Cleaver O

Melton D

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.1064344

Published

2001-10-19

Epub

2001-00-27

Pages

564-7

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 11577202

External Links

PubMed source DOI: 10.1126/science.1064344 View journal details

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Induction of pancreatic differentiation by signals from blood vessels.

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