MOLECULAR EVENTS IN AIRWAY CILIATED CELL DIFFERENTIATION DURING DEVELOPMENT

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Ciliated cells of airways surface epithelium function to clear inhaled particles and mucous secretions from the lungs. Either a low density of ciliated cells or aberrations in ciliary ultrastructure can impair mucociliary clearance. Although the morphology of airway ciliation during maturation and repair has been described, little is known about the molecular events involved in ciliogenesis. In humans, airway ciliation occurs prenatally; however, the majority of ciliation occurs postnatally in the ferret which has become an important study model. In these studies, we will identify or clone molecular markers for studying ciliogenesis. We will focus on three possible markers: the influenza virus receptor microtubules and dynein which is the enzyme responsible for ciliary motility. We will characterize the expression of the mRNAs for these markers at different maturational stages in the infant ferret using Northern hybridization and in situ hybridization analyses. These studies will then be carried out in ferrets after injury to the airways to determine if reciliation after injury is different from ciliation during normal development. Finally, we use these probes and techniques to define ciliation in human airways both during normal fetal maturation and following injury. These studies will be coordinated with analysis of ultrastructural features to determine the sequence of ultrastructural and morphologic events in ciliogenesis. We hypothesize that the molecular events in ciliogenesis occur in an orderly sequence and that aberrations in cilia noted after injury can be explained by interference with this process.