Wnt5 Signaling in Vertebrate Pancreas Development

BMC Biol. 2005 Oct 24;3:23. doi: 10.1186/1741-7007-3-23.

Abstract

Background: Signaling by the Wnt family of secreted glycoproteins through their receptors, the frizzled (Fz) family of seven-pass transmembrane proteins, is critical for numerous cell fate and tissue polarity decisions during development.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Movement
  • Embryo, Nonmammalian / physiology
  • Frizzled Receptors
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Insulin / genetics
  • Islets of Langerhans / embryology
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Pancreas / embryology*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology*
  • Receptors, G-Protein-Coupled / genetics*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Transcription, Genetic
  • Transfection
  • Vertebrates / embryology*
  • Vertebrates / growth & development
  • Wnt Proteins / genetics*
  • Wnt Proteins / physiology
  • Wnt-5a Protein
  • Xenopus
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / physiology*

Substances

  • Frizzled Receptors
  • Insulin
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, zebrafish
  • Zebrafish Proteins
  • fzd2 protein, zebrafish