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This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 296/6/L1067    most recent 00001.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Francis, R. J. B. Articles by Lo, C. W. PubMed PubMed Citation Articles by Francis, R. J. B. Articles by Lo, C. W.

Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway

¹Laboratory of Developmental Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; and ²Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg; and ³Department of Tumor Virology, German Cancer Research Center, Heidelberg, Germany

Submitted 5 January 2009 ; accepted in final form 27 March 2009

Mucociliary clearance in the adult trachea is well characterized, but there are limited data in newborns. Cilia-generated flow was quantified across longitudinal sections of mouse trachea from birth through postnatal day (PND) 28 by tracking fluorescent microsphere speed and directionality. The percentage of ciliated tracheal epithelial cells, as determined by immunohistochemistry, was shown to increase linearly between PND 0 and PND 21 (R² = 0.94). While directionality measurements detected patches of flow starting at PND 3, uniform flow across the epithelia was not observed until PND 7 at a 35% ciliated cell density. Flow became established at a maximal rate at PND 9 and beyond. A linear correlation was observed between the percentage of ciliated cells versus flow speed (R² = 0.495) and directionality (R² = 0.975) between PND 0 and PND 9. Cilia beat frequency (CBF) was higher at PND 0 than at all subsequent time points, but cilia beat waveform was not noticeably different. Tracheal epithelia from a mouse model of primary ciliary dyskinesia (PCD) harboring a Mdnah5 mutation showed that ciliated cell density was unaffected, but no cilia-generated flow was detected. Cilia in mutant airways were either immotile or with slow dyssynchronous beat and abnormal ciliary waveform. Overall, our studies showed that the initiation of cilia-generated flow is directly correlated with an increase in epithelial ciliation, with the measurement of directionality being more sensitive than speed for detecting flow. The higher CBF observed in newborn epithelia suggests unique physiology in the newborn trachea, indicating possible clinical relevance to the pathophysiology of respiratory distress seen in newborn PCD patients.

ciliogenesis; development; murine model; primary ciliary dyskinesia; trachea