Bbof1 is required to maintain cilia orientation

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.

[1]  M. Scott,et al.  Microtubules Enable the Planar Cell Polarity of Airway Cilia , 2012, Current Biology.

[2]  E. Houliston,et al.  A conserved function for Strabismus in establishing planar cell polarity in the ciliated ectoderm during cnidarian larval development , 2012, Development.

[3]  M. Werner,et al.  Understanding ciliated epithelia: The power of Xenopus , 2012, Genesis.

[4]  T. Noda,et al.  Coordinated Ciliary Beating Requires Odf2-Mediated Polarization of Basal Bodies via Basal Feet , 2012, Cell.

[5]  J. D. Axelrod,et al.  Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation , 2011, Nature Cell Biology.

[6]  Clare C. Yu,et al.  Actin and microtubules drive differential aspects of planar cell polarity in multiciliated cells , 2011, The Journal of cell biology.

[7]  J. Axelrod,et al.  Pointing in the right direction: new developments in the field of planar cell polarity , 2011, Nature Reviews Genetics.

[8]  J. Wallingford,et al.  Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. , 2011, Genes & development.

[9]  K. Sawamoto,et al.  Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia , 2010, Nature Cell Biology.

[10]  Clare C. Yu,et al.  The PCP Pathway Instructs the Planar Orientation of Ciliated Cells in the Xenopus Larval Skin , 2009, Current Biology.

[11]  J. C. Belmonte,et al.  The Forkhead protein, FoxJ1, specifies node-like cilia in Xenopus and Zebrafish embryos , 2008, Nature Genetics.

[12]  Tae Joo Park,et al.  Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells , 2008, Nature Genetics.

[13]  W. Marshall,et al.  Cilia orientation and the fluid mechanics of development. , 2008, Current opinion in cell biology.

[14]  Jennifer A Zallen,et al.  Planar Polarity and Tissue Morphogenesis , 2007, Cell.

[15]  S. Chien,et al.  A positive feedback mechanism governs the polarity and motion of motile cilia , 2007, Nature.

[16]  Tiansen Li,et al.  Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells. , 2005, Molecular biology of the cell.

[17]  M. Sanderson,et al.  The Ciliary Rootlet Maintains Long-Term Stability of Sensory Cilia , 2005, Molecular and Cellular Biology.

[18]  Tiansen Li,et al.  Rootletin, a novel coiled-coil protein, is a structural component of the ciliary rootlet , 2002, The Journal of cell biology.

[19]  D. Wettstein,et al.  A two-step mechanism generates the spacing pattern of the ciliated cells in the skin of Xenopus embryos. , 1999, Development.

[20]  Kurt E. Johnson,et al.  Normal Table of Xenopus Laevis , 1968, The Yale Journal of Biology and Medicine.

[21]  W. Marshall,et al.  Basal bodies platforms for building cilia. , 2008, Current topics in developmental biology.

[22]  Wallace F. Marshall,et al.  Chapter 1 Basal Bodies , 2008 .

[23]  R. Harland,et al.  Early development of Xenopus laevis : a laboratory manual , 2000 .

[24]  J. Faber,et al.  Normal table of Xenopus laevis. , 1994 .

[25]  R. Gordon Three-dimensional organization of microtubules and microfilaments of the basal body apparatus of ciliated respiratory epithelium. , 1982, Cell motility.