title: Bbof1 is required to maintain cilia orientation.
abstract: 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.
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Chien
authors.forename: Michael E
authors.initials: ME
authors.lastname: Werner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stubbs
authors.forename: Matt S
authors.initials: MS
authors.lastname: Joens
authors.forename: Julie
authors.initials: J
authors.lastname: Li
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
authors.forename: James A J
authors.initials: JA
authors.lastname: Fitzpatrick
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Mitchell
authors.forename: Chris
authors.initials: C
authors.lastname: Kintner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D054468:Axoneme / Q000378:metabolism; D019521:Body Patterning; D002454:Cell Differentiation; D002923:Cilia / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057446:Hydrodynamics; D009068:Movement; D015739:Nocodazole / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000378:metabolism* / Q000502:physiology
chemical_list: D000199:Actins; C490956:FOXJ1 protein, Xenopus; D051858:Forkhead Transcription Factors; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D015739:Nocodazole
keywords: Cilia; Planar cell polarity; Xenopus
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