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Nodal and lefty signaling regulates the growth of pancreatic cells
Author(s) -
Zhang YouQing,
Sterling Lori,
Stotland Aleksandr,
Hua Hong,
Kritzik Marcie,
Sarvetnick Nora
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21527
Subject(s) - nodal , biology , nodal signaling , microbiology and biotechnology , activin receptor , medicine , endocrinology , islet , signal transduction , embryogenesis , embryo , anatomy , gastrulation , insulin
Nodal and its antagonist, Lefty, are important mediators specifying the laterality of the organs during embryogenesis. Nodal signals through activin receptors in the presence of its co‐receptor, Cripto. In the present study, we investigated the possible roles of Nodal and Lefty signaling during islet development and regeneration. We found that both Nodal and Lefty are expressed in the pancreas during embryogenesis and islet regeneration. In vitro studies demonstrated that Nodal inhibits, whereas Lefty enhances, the proliferation of a pancreatic cell line. In addition, we showed that Lefty‐1 activates MAPK and Akt phosphorylation in these cells. In vivo blockade of endogenous Lefty using neutralizing Lefty‐1 monoclonal antibody results in a significantly decreased proliferation of duct epithelial cells during islet regeneration. This is the first study to decipher the expression and function of Nodal and Lefty in pancreatic growth. Importantly, our results highlight a novel function of Nodal‐Lefty signaling in the regulation of expansion of pancreatic cells. Developmental Dynamics 237:1255‐1267, 2008. © 2008 Wiley‐Liss, Inc.