Wnt5 signaling in vertebrate pancreas development

We report a novel role of Wnt signaling in organogenesis using the formation of the islet during pancreatic development as a model tissue. We used the advantages of the zebrafish to visualize and document this process in living embryos and demonstrated that insulin-positive cells actively migrate to form an islet. We used morpholinos (MOs), sequence-specific translational inhibitors, and time-lapse imaging analysis to show that the Wnt-5 ligand and the Fz-2 receptor are required for proper insulin-cell migration in zebrafish. Histological analyses of islets in Wnt5a-/- mouse embryos showed that Wnt5a signaling is also critical for murine pancreatic insulin-cell migration.Our results implicate a conserved role of a Wnt5/Fz2 signaling pathway in islet formation during pancreatic development. This study opens the door for further investigation into a role of Wnt signaling in vertebrate organ development and disease.Wnt signaling pathways play important roles in both normal development and in the pathogenesis of a variety of diseases, including cancer [1]. Activation of a Wnt signaling pathway requires interaction between a secreted glycoprotein, Wnt, and a seven-pass transmembrane receptor protein, Frizzled (Fz). Different combinations of Wnt and Fz ligand-receptor pairs can transduce at least three distinct kinds of intracellular signaling pathways. The "canonical" Wnt signaling pathway (Wnt/β-catenin pathway) results in changes of intracellular β-catenin levels and is thought to be involved in cell fate specification and proliferation. Wnt pathway activation can also lead to changes in either intracellular Ca2+ concentration (Wnt/Ca2+ pathway) or actin cytoskeleton reorganization (Wnt/tissue polarity pathway) [2]. The role(s) of these 'non-canonical' Wnt signaling pathway(s) in organ formation are largely unknown.A function for Wnt signaling has been suggested by the expression patterns of Wnt and Fz genes during development of the mouse embryonic pancreas [3]. At em