Wnt signaling is required for organization of the lens fiber cell cytoskeleton and development of lens three-dimensional architecture.

Wnt signaling is required for organization of the lens fiber cell cytoskeleton and development of lens three-dimensional architecture.
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DOI:
10.1016/j.ydbio.2008.09.002
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发表时间:
2008-12-01
影响因子:
2.7
通讯作者:
McAvoy, John W.
McAvoy, John W.
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Yongjuan;Stump, Richard J. W.;Lovicu, Frank J.;Shimono, Akihiko;McAvoy, John W.

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一个器官如何发展其特征形状是一个主要问题。这对于眼睛透镜尤其重要,因为其功能取决于具有适当有序的三维细胞结构。最近的体外研究表明,Wnt信号在调节哺乳动物透镜中FGF诱导的纤维细胞分化的形态学事件中起关键作用。为了进一步研究这一点,在转基因小鼠的透镜纤维细胞中过表达Wnt信号传导拮抗剂分泌卷曲相关蛋白2(Sfrp 2)。在这些小鼠中,纤维细胞伸长减弱,单个纤维呈现不规则的形状,因此没有对齐或包装规则;微管,微丝和中间丝在这些纤维中明显无序。此外,转基因晶状体的一个显著特征是,纤维没有发展出正常晶状体中常见的凸曲率。这似乎与缺乏所需的直接迁移活动在其顶端和基部的尖端,以及形成联锁过程沿着其侧缘的膨胀过程。Wnt/平面细胞极性(PCP)途径的组分被下调或抑制。总之,这支持了Wnt/PCP信号在协调纤维细胞细胞骨架的复杂组织和动力学中的作用。
How an organ develops its characteristic shape is a major issue. This is particularly critical for the eye lens as its function depends on having appropriately ordered three-dimensional cellular architecture. Recent in vitro studies indicate that Wnt signaling plays key roles in regulating morphological events in FGF-induced fiber cell differentiation in the mammalian lens. To further investigate this the Wnt signaling antagonist, secreted frizzled-related protein 2 (Sfrp2), was overexpressed in lens fiber cells of transgenic mice. In these mice fiber cell elongation was attenuated and individual fibers exhibited irregular shapes and consequently did not align or pack regularly; microtubules, microfilaments and intermediate filaments were clearly disordered in these fibers. Furthermore, a striking feature of transgenic lenses was that fibers did not develop the convex curvature typically seen in normal lenses. This appears to be related to lack of protrusive processes that are required for directed migratory activity at their apical and basal tips as well as for the formation of interlocking processes along their lateral margins. Components of the Wnt/Planar Cell Polarity (PCP) pathway were downregulated or inhibited. Taken together this supports a role for Wnt/PCP signaling in orchestrating the complex organization and dynamics of the fiber cell cytoskeleton.
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