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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 6, December, 2000 734-741

Characterization of an Axonemal Dynein Heavy Chain Expressed Early in Airway Epithelial Ciliogenesis

William Reed, Johnny L. Carson, Billie M. Moats-Staats, Thomas Lucier, Ping-chuan Hu, Luisa Brighton, Todd M. Gambling, Chien-Hui Huang, Margaret W. Leigh, and Albert M. Collier

Departments of Pediatrics and Cell Biology and Anatomy, The Center for Environmental Medicine and Lung Biology, and the Frank Porter Graham Child Development Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

The most conspicuous evidence of airway epithelial maturation and vitality is the presence of motile cilia. In an effort to generate genetic and antigenic markers of airway maturation, injury, and repair, we characterized airway epithelial expression of a gene identified by two human expressed sequence tags that encoded peptides with sequence similarity to an invertebrate ciliary dynein heavy chain (DHC). Molecular analyses showed that the gene has a very large RNA transcript that encodes a very high molecular weight polypeptide with biochemical properties that are characteristic of a dynein heavy chain. Expression of the gene transcript correlated with the presence of ciliated cells in tissues, and immunohistochemical localization of the gene product confirmed its presence in the cilia of mature airway epithelium. In epithelium undergoing ciliogenesis ex vivo, expression of the gene transcript preceded ciliation of the epithelium and the gene product was present in the cytoplasm and at the apical border of nonciliated cells. These data suggested that the gene encodes an axonemal DHC that is expressed early during ciliogenesis, before the appearance of cilia.




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