Bbof1 is required to maintain cilia orientation
Bbof1 is required to maintain cilia orientation
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DOI：
10.1242/dev.096727
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发表时间：
2013-08-15
期刊：
影响因子：
4.6
通讯作者：
Kintner, Chris
中科院分区：
文献类型：
--
作者：
Chien, Yuan-Hung;Werner, Michael E.;Kintner, Chris
多纤毛细胞 (MCC) 是高度特化的上皮细胞，利用数百个活动纤毛在各种器官系统中产生旺盛的定向流动。这种流动的产生需要建立平面细胞极性（PCP），从而 MCC 沿着共同的平面轴排列数百个跳动的纤毛。已知 MCC 中纤毛的平面轴是通过 PCP 途径和流体动力学线索建立的，但纤毛定向所需的下游步骤仍不清楚。在这里，我们基于对一种未表征的卷曲螺旋蛋白（称为 bbof1）的表型分析，描述了纤毛方向的一个新组成部分。我们发现 bbof1 的表达是在 MCC 分化的早期阶段由主调节因子 Foxj1 诱导的。 MCC 分化和纤毛发生通常发生在 bbof1 活性降低的胚胎中，但纤毛方向严重破坏。我们发现 bbof1 突变体中的纤毛仍然可以对图案和流体动力学线索做出反应，但缺乏保持其精确方向的能力。 bbof1 的错误表达会促进纤毛排列，即使在没有流动的情况下或在微管和肌动蛋白丝被破坏的胚胎中也是如此。 Bbof1 似乎通过定位于邻近基体的极性结构来介导纤毛排列。总之，这些结果表明 bbof1 是 MCC 中对齐和维持纤毛方向以响应流动所需的基底体成分。
Multiciliate cells (MCCs) are highly specialized epithelial cells that employ hundreds of motile cilia to produce a vigorous directed flow in a variety of organ systems. The production of this flow requires the establishment of planar cell polarity (PCP) whereby MCCs align hundreds of beating cilia along a common planar axis. The planar axis of cilia in MCCs is known to be established via the PCP pathway and hydrodynamic cues, but the downstream steps required for cilia orientation remain poorly defined. Here, we describe a new component of cilia orientation, based on the phenotypic analysis of an uncharacterized coiled-coil protein, called bbof1. We show that the expression of bbof1 is induced during the early phases of MCC differentiation by the master regulator foxj1. MCC differentiation and ciliogenesis occurs normally in embryos where bbof1 activity is reduced, but cilia orientation is severely disrupted. We show that cilia in bbof1 mutants can still respond to patterning and hydrodynamic cues, but lack the ability to maintain their precise orientation. Misexpression of bbof1 promotes cilia alignment, even in the absence of flow or in embryos where microtubules and actin filaments are disrupted. Bbof1 appears to mediate cilia alignment by localizing to a polar structure adjacent to the basal body. Together, these results suggest that bbof1 is a basal body component required in MCCs to align and maintain cilia orientation in response to flow.