Wnt5 signaling in vertebrate pancreas development.
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.


CONCLUSIONS
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.
Kim
Hyon J
HJ
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA. kimx0183@umn.edu
Schleiffarth
Jack R
JR
Jessurun
Jose
J
Sumanas
Saulius
S
Petryk
Anna
A
Lin
Shuo
S
Ekker
Stephen C
SC
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D004625:Embryo, Nonmammalian / Q000502:physiology; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D010179:Pancreas / Q000196:embryology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D014714:Vertebrates / Q000196:embryology* / Q000254:growth & development; D051153:Wnt Proteins / Q000235:genetics* / Q000502:physiology; D000071818:Wnt-5a Protein; D014981:Xenopus; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
D051157:Frizzled Receptors; D007328:Insulin; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C480282:Wnt5a protein, zebrafish; D029961:Zebrafish Proteins; C510284:fzd2 protein, zebrafish