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Nodal and lefty signaling regulates the growth of pancreatic cells

You-Qing Zhang1, Lori Sterling, Aleksandr Stotland

  • 1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|April 9, 2008
PubMed

Insights

Nodal and Lefty signaling regulate pancreatic cell expansion. Lefty promotes pancreatic cell proliferation, while Nodal inhibits it, impacting islet development and regeneration.

Area of Science:

  • Developmental Biology
  • Endocrinology
  • Cell Signaling

Background:

  • Nodal and Lefty are crucial for organ laterality during embryogenesis.
  • Nodal signaling involves activin receptors and the co-receptor Cripto.
  • The roles of Nodal and Lefty in pancreatic islet development and regeneration are largely unknown.

Purpose of the Study:

  • To investigate the expression and function of Nodal and Lefty in pancreatic islet development and regeneration.
  • To elucidate the signaling pathways modulated by Lefty in pancreatic cells.
  • To assess the impact of Lefty blockade on pancreatic cell proliferation in vivo.

Main Methods:

  • Expression analysis of Nodal and Lefty in pancreatic tissues.
  • In vitro studies using a pancreatic cell line to assess proliferation and signaling.
  • In vivo experiments using neutralizing Lefty-1 monoclonal antibodies.

Main Results:

  • Nodal and Lefty are expressed in the pancreas during embryogenesis and regeneration.
  • Nodal inhibited pancreatic cell proliferation in vitro, while Lefty enhanced it.
  • Lefty-1 activated MAPK and Akt phosphorylation in pancreatic cells.
  • Lefty blockade in vivo significantly reduced duct epithelial cell proliferation during regeneration.

Conclusions:

  • Nodal-Lefty signaling plays a significant role in pancreatic cell expansion.
  • Lefty promotes pancreatic cell proliferation through MAPK and Akt pathways.
  • This study reveals a novel function for Nodal-Lefty signaling in regulating pancreatic growth and regeneration.

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