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Letter
Nature 447, 97-101 (3 May 2007) | doi:10.1038/nature05771; Received 22 December 2006; Accepted 16 March 2007; Published online 22 April 2007
A positive feedback mechanism governs the polarity and motion of motile cilia
Brian Mitchell1, Richard Jacobs1,2, Julie Li3, Shu Chien3 & Chris Kintner1
- The Salk Institute for Biological Studies, La Jolla, California 92186, USA
- Howard Hughes Medical Institute, USA
- Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California 92093, USA
Correspondence to: Chris Kintner1 Correspondence and requests for materials should be addressed to C.K. (Email: kintner@salk.edu).
Abstract
Ciliated epithelia produce fluid flow in many organ systems, ranging from the respiratory tract where it clears mucus1 to the ventricles of the brain where it transports cerebrospinal fluid2. 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 infertility3. 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 system4. 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.
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