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Am J Physiol Lung Cell Mol Physiol 286: L650-L657, 2004. First published June 20, 2003; doi:10.1152/ajplung.00170.2003
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Stem Cells in Lung Biology

Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells

Yingjian You,1 Tao Huang,1 Edward J. Richer,1 Jens-Erik Harboe Schmidt,2 Joseph Zabner,3 Zea Borok,4 and Steven L. Brody1,5

1Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; 2Department of Biochemistry and Molecular Biology and Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033; 3Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242; and 4Department of Medicine and Will Rogers Institute Pulmonary Research Center, University of Southern California, Los Angeles, California 90033

Submitted 29 May 2003 ; accepted in final form 11 June 2003

Factors required for commitment of an undifferentiated airway epithelial cell to a ciliated cell are unknown. Cell ultrastructure analysis indicates ciliated cell commitment activates a multistage program involving synthesis of cilia precursor proteins and assembly of macromolecular complexes. Foxj1 is an f-box transcription factor expressed in ciliated cells and shown to be required for cilia formation by gene deletion in a mouse model. To identify a specific role for foxj1 in directing the ciliated cell phenotype, we evaluated the capacity of foxj1 to induce ciliogenesis and direct cilia assembly. In a primary culture model of wild-type mouse airway epithelial cells, foxj1 expression preceded the appearance of cilia and in cultured foxj1 null cells cilia did not develop. Delivery of foxj1 to polarized epithelial cell lines and primary cultured alveolar epithelial cells failed to promote ciliogenesis. Similarly, delivery of foxj1 to wild-type airway epithelial cells did not enhance the total number of ciliated cells. In contrast, delivery of foxj1 to null cells resulted in the appearance of cilia. Analysis revealed that, in the absence of foxj1, null cells contained cilia precursor basal bodies, indicating prior commitment to ciliogenesis. However, the basal bodies were disorganized within the apical compartment and failed to dock with the apical membrane. Reconstitution of foxj1 in null cells restored normal basal body organization, resulting in axoneme growth. Thus foxj1 functions in late-stage ciliogenesis to regulate programs promoting basal body docking and axoneme formation in cells previously committed to the ciliated cell phenotype.

airway; basal body; cilia; differentiation; mouse


Address for reprint requests and other correspondence: Steven L. Brody, Washington Univ. School of Medicine, Campus Box 8052, 660 South Euclid Ave., St. Louis, MO 63110 (E-mail: brodys{at}msnotes.wustl.edu.)




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