Wnt signaling enhances FGF2-triggered lens fiber cell differentiation
Wnt signaling enhances FGF2-triggered lens fiber cell differentiation
复制标题
DOI：
10.1242/dev.01060
复制
发表时间：
2004-04-01
期刊：
影响因子：
4.6
通讯作者：
Joo, CK
中科院分区：
文献类型：
--
作者：
Lyu, J;Joo, CK
Wnt信号转导参与许多发育过程，包括细胞命运的改变。已知Wnt家族的几个成员以及参与Wnt信号传导的其他分子，包括Frizzled受体、LDL相关蛋白共受体、Dishevelled和Dickkopf家族的成员，在胚胎或胚后发育期间在透镜中表达。然而，Wnt信号转导在透镜纤维分化中的功能仍不清楚。在这里，我们发现GSK-3 β激酶失活，β-连环蛋白积累在透镜纤维细胞分化的早期阶段。在外植体培养系统中，Wnt条件培养基（CM）诱导β-晶体蛋白，纤维细胞分化的标志物，积累，而不改变细胞形状。相反，在用FGF引发后用Wnt刺激的上皮细胞延长，积累β-晶体蛋白、水通道蛋白-0、p57 kip 2，并改变其钙粘蛋白的表达。用稳定β-连环蛋白的锂处理诱导β-晶状体蛋白的积累，但是在FGF引发后用锂处理的外植体不像Wnt应用后那样伸长。这些结果表明，Wnt促进纤维细胞分化的形态学方面的过程中，需要FGF信号，但独立于β-连环蛋白。Wnt信号在透镜上皮细胞向纤维细胞分化中可能起重要作用。
Wnt signaling is implicated in many developmental processes, including cell fate changes. Several members of the Wnt family, as well as other molecules involved in Wnt signaling, including Frizzled receptors, LDL-related protein co-receptors, members of the Dishevelled and Dickkopf families, are known to be expressed in the lens during embryonic or postembryonic development. However, the function of Wnt signaling in lens fiber differentiation remains unknown. Here, we show that GSK-3beta kinase is inactivated and that beta-catenin accumulates during the early stages of lens fiber cell differentiation. In an explant culture system, Wnt conditioned medium (CM) induced the accumulation of beta-crystallin, a marker of fiber cell differentiation, without changing cell shape. In contrast, epithelial cells stimulated with Wnt after priming with FGF elongated, accumulated beta-crystallin, aquaporin-0, p57kip2, and altered their expression of cadherins. Treatment with lithium, which stabilizes beta-catenin, induced the accumulation of beta-crystallin, but explants treated with lithium after FGF priming did not elongate as they did after Wnt application. These results show that Wnts promote the morphological aspects of fiber cell differentiation in a process that requires FGF signaling, but is independent of beta-catenin. Wnt signaling may play an important role in lens epithelial-to-fiber differentiation.