Kim Hyon J, Schleiffarth Jack R, Jessurun Jose, Sumanas Saulius, Petryk Anna, Lin Shuo, Ekker Stephen C
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
BMC Biol. 2005 Oct 24;3:23. doi: 10.1186/1741-7007-3-23.
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.
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.
分泌型糖蛋白Wnt家族通过其受体——七次跨膜蛋白卷曲蛋白（Fz）家族进行信号传导，这对于发育过程中众多细胞命运和组织极性的决定至关重要。
我们以胰腺发育过程中胰岛的形成为模型组织，报道了Wnt信号在器官发生中的新作用。我们利用斑马鱼的优势，在活体胚胎中可视化并记录这一过程，证明胰岛素阳性细胞会主动迁移形成胰岛。我们使用吗啉代寡核苷酸（MOs）、序列特异性翻译抑制剂和延时成像分析，表明Wnt-5配体和Fz-2受体对于斑马鱼中胰岛素细胞的正常迁移是必需的。对Wnt5a基因敲除小鼠胚胎胰岛的组织学分析表明，Wnt5a信号传导对于小鼠胰腺胰岛素细胞的迁移也至关重要。
我们的结果表明Wnt5/Fz2信号通路在胰腺发育过程中胰岛形成方面具有保守作用。这项研究为进一步探究Wnt信号在脊椎动物器官发育和疾病中的作用打开了大门。
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