Mitchell Brian, Jacobs Richard, Li Julie, Chien Shu, Kintner Chris
The Salk Institute for Biological Studies, La Jolla, California 92186, USA.
Nature. 2007 May 3;447(7140):97-101. doi: 10.1038/nature05771. Epub 2007 Apr 22.
Ciliated epithelia produce fluid flow in many organ systems, ranging from the respiratory tract where it clears mucus to the ventricles of the brain where it transports cerebrospinal fluid. Human diseases that disable ciliary flow, such as primary ciliary dyskinesia, can compromise organ function or the ability to resist pathogens, resulting in recurring respiratory infections, otitis, hydrocephaly and infertility. To create a ciliary flow, the cilia within each cell need to be polarized coordinately along the planar axis of the epithelium, but how polarity is established in any ciliated epithelia is not known. Here we analyse the developmental mechanisms that polarize cilia, using the ciliated cells in the developing Xenopus larval skin as a model system. We show that cilia acquire polarity through a sequence of events, beginning with a polar bias set by tissue patterning, followed by a refinement phase. Our results indicate that during refinement, fluid flow is both necessary and sufficient in determining cilia polarity. These findings reveal a novel mechanism in which tissue patterning coupled with fluid flow act in a positive feedback loop to direct the planar polarity of cilia.
纤毛上皮在许多器官系统中产生液体流动，从清除黏液的呼吸道到运输脑脊液的脑室。导致纤毛流动功能障碍的人类疾病，如原发性纤毛运动障碍，会损害器官功能或抵抗病原体的能力，导致反复的呼吸道感染、中耳炎、脑积水和不孕。为了产生纤毛流动，每个细胞内的纤毛需要沿着上皮的平面轴协调极化，但在任何纤毛上皮中极性是如何建立的尚不清楚。在这里，我们以非洲爪蟾幼体皮肤中发育的纤毛细胞为模型系统，分析使纤毛极化的发育机制。我们表明，纤毛通过一系列事件获得极性，始于由组织模式设定的极性偏向，随后是一个细化阶段。我们的结果表明，在细化过程中，液体流动对于确定纤毛极性既是必要的也是充分的。这些发现揭示了一种新机制，即组织模式与液体流动在一个正反馈回路中起作用，以指导纤毛的平面极性。
