PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates
PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates
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DOI：
10.1038/nature02677
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发表时间：
2004-07-01
期刊：
影响因子：
64.8
通讯作者：
Tessier-Lavigne, M
中科院分区：
文献类型：
--
作者：
Lu, XW;Borchers, AGM;Tessier-Lavigne, M
除了在上皮细胞中起作用的顶端-基底极性途径之外，平面细胞极性（PCP）途径在上皮组织平面内建立极性，并且从果蝇到哺乳动物都是保守的。在果蝇中，PCP基因的“核心”组包括卷曲（fz）、火烈鸟/星夜、凌乱（dsh）、货车高/斜视和刺痒，其功能是调节翅毛、刚毛和小眼极性（1-3）。在脊椎动物中，PCP通路调节会聚性伸展运动和神经管闭合（3-5），以及内耳中感觉毛细胞的静纤毛束的方向（6）。在这里，我们发现小鼠蛋白酪氨酸激酶7（PTK 7）基因（编码一种具有酪氨酸激酶同源性的进化上保守的跨膜蛋白）的突变破坏了神经管闭合和静纤毛束定向，并显示了与小鼠货车Gogh同源物vangl突变的遗传相互作用（2）。我们还表明，PTK 7是动态本地化毛细胞极化过程中，和非洲爪蟾的同源物PTK 7是所需的神经会聚延伸和神经管关闭。这些结果将PTK 7确定为脊椎动物中五氯苯酚的新型调节剂。
In addition to the apical-basal polarity pathway operating in epithelial cells, a planar cell polarity (PCP) pathway establishes polarity within the plane of epithelial tissues and is conserved from Drosophila to mammals. In Drosophila, a 'core' group of PCP genes including frizzled (fz), flamingo/starry night, dishevelled (dsh), Van Gogh/strabismus and prickle, function to regulate wing hair, bristle and ommatidial polarity(1-3). In vertebrates, the PCP pathway regulates convergent extension movements and neural tube closure(3-5), as well as the orientation of stereociliary bundles of sensory hair cells in the inner ear(6). Here we show that a mutation in the mouse protein tyrosine kinase 7 (PTK7) gene, which encodes an evolutionarily conserved transmembrane protein with tyrosine kinase homology, disrupts neural tube closure and stereociliary bundle orientation, and shows genetic interactions with a mutation in the mouse Van Gogh homologue vangl(2). We also show that PTK7 is dynamically localized during hair cell polarization, and that the Xenopus homologue of PTK7 is required for neural convergent extension and neural tube closure. These results identify PTK7 as a novel regulator of PCP in vertebrates.