Endothelial Cell Promotion of Early Liver and Pancreas Development

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. Deborah A. Freedman,
  2. Yasushige Kashima and
  3. Kenneth S. Zaret

Published Online: 11 SEP 2007

DOI: 10.1002/9780470319413.ch16

Vascular Development: Novartis Foundation Symposium 283

Vascular Development: Novartis Foundation Symposium 283

How to Cite

Freedman, D. A., Kashima, Y. and Zaret, K. S. (2007) Endothelial Cell Promotion of Early Liver and Pancreas Development, in Vascular Development: Novartis Foundation Symposium 283 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470319413.ch16

Author Information

  1. Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA

Publication History

  1. Published Online: 11 SEP 2007
  2. Published Print: 20 JUL 2007

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470034286

Online ISBN: 9780470319413

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Keywords:

  • Pancreas;
  • liver;
  • endoderm;
  • mesoderm;
  • organogenesis;
  • specification;
  • tissue induction;
  • determination;
  • morphogenesis;
  • endothelial cells

Summary

Different steps of embryonic pancreas and liver development require inductive signals from endothelial cells. During liver development, interactions between newly specified hepatic endoderm cells and nascent endothelial cells are crucial for the endoderm's subsequent growth and morphogenesis into a liver bud. Reconstitution of endothelial cell stimulation of hepatic cell growth with embryonic tissue explants demonstrated that endothelial signalling occurs independent of the blood supply. During pancreas development, midgut endoderm interactions with aortic endothelial cells induce Ptf1a, a crucial pancreatic determinant. Endothelial cells also have a later effect on pancreas development, by promoting survival of the dorsal mesenchyme, which in turn produces factors supporting pancreatic endoderm. A major goal of our laboratory is to determine the endothelial-derived molecules involved in these inductive events. Our data show that cultured endothelial cells induce Ptf1a in dorsal endoderm explants lacking an endogenous vasculature. We are purifying endothelial cell line product(s) responsible for this effect. We are also identifying endothelial-responsive regulatory elements in genes such as Ptf1a by genetic mapping and chromatin-based assays. These latter approaches will allow us to track endothelial-responsive signal pathways from DNA targets within progenitor cells. The diversity of organogenic steps dependent upon endothelial cell signalling suggests that cross-regulation of tissue development with its vasculature is a general phenomenon.