The role of frizzled3 and frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells
The role of frizzled3 and frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells
复制标题
DOI：
10.1523/jneurosci.4698-05.2005
复制
发表时间：
2006-02-22
影响因子：
5.3
通讯作者：
Nathans, J
中科院分区：
文献类型：
--
作者：
Wang, YH;Guo, NN;Nathans, J
在小鼠中，Frizzled3 (Fz3) 和 Frizzled6 (Fz6) 先前已被证明可以分别控制中枢神经系统的轴突生长和引导以及皮肤中的毛发图案。在这里，我们报告 Fz3 和 Fz6 冗余地控制听觉和前庭感觉细胞子集上的神经管闭合和毛束的平面方向。在内耳中，Fz3 和 Fz6 蛋白以与平面极性轴相关的模式定位于所有感觉上皮中感觉和支持细胞的侧面。有趣的是，Fz6 定位相对于动纤毛不对称位置的极性在半规管嵴中的前庭毛细胞和柯蒂氏器中的听毛细胞之间是相反的。 Vangl2 是果蝇平面细胞极性 (PCP) 基因 van Gogh/Strabismus 的两个哺乳动物同源物之一，也是听觉感觉细胞子集和所有前庭感觉细胞上正确毛束方向所必需的。在 Vangl2 突变体（Looptail；Lp）的内耳中，Fz3 和 Fz6 蛋白积累到正常水平，但不能正确定位在细胞表面。这些结果支持这样的观点，即脊椎动物和无脊椎动物使用相似的分子机制来控制多种五氯苯酚依赖性发育过程。这项研究还确立了前庭感觉上皮作为分析 PCP 的易处理组织，并介绍了使用遗传镶嵌来确定哺乳动物中 PCP 蛋白的绝对方向。
In the mouse, Frizzled3 (Fz3) and Frizzled6 (Fz6) have been shown previously to control axonal growth and guidance in the CNS and hair patterning in the skin, respectively. Here, we report that Fz3 and Fz6 redundantly control neural tube closure and the planar orientation of hair bundles on a subset of auditory and vestibular sensory cells. In the inner ear, Fz3 and Fz6 proteins are localized to the lateral faces of sensory and supporting cells in all sensory epithelia in a pattern that correlates with the axis of planar polarity. Interestingly, the polarity of Fz6 localization with respect to the asymmetric position of the kinocilium is reversed between vestibular hair cells in the cristae of the semicircular canals and auditory hair cells in the organ of Corti. Vangl2, one of two mammalian homologs of the Drosophila planar cell polarity (PCP) gene van Gogh/Strabismus, is also required for correct hair bundle orientation on a subset of auditory sensory cells and on all vestibular sensory cells. In the inner ear of a Vangl2 mutant (Looptail; Lp), Fz3 and Fz6 proteins accumulate to normal levels but do not localize correctly at the cell surface. These results support the view that vertebrates and invertebrates use similar molecular mechanisms to control a wide variety of PCP-dependent developmental processes. This study also establishes the vestibular sensory epithelium as a tractable tissue for analyzing PCP, and it introduces the use of genetic mosaics for determining the absolute orientation of PCP proteins in mammals.