Quantitative optical coherence tomography imaging of intermediate flow defect phenotypes in ciliary physiology and pathophysiology.
Cilia-driven fluid flow is a critical yet poorly understood aspect of pulmonary physiology. Here, we demonstrate that optical coherence tomography-based particle tracking velocimetry can be used to quantify subtle variability in cilia-driven flow performance in Xenopus, an important animal model of ciliary biology. Changes in flow performance were quantified in the setting of normal development, as well as in response to three types of perturbations: mechanical (increased fluid viscosity), pharmacological (disrupted serotonin signaling), and genetic (diminished ciliary motor protein expression). Of note, we demonstrate decreased flow secondary to gene knockdown of kif3a, a protein involved in ciliogenesis, as well as a dose-response decrease in flow secondary to knockdown of dnah9, an important ciliary motor protein.
Yale University, Department of Biomedical Engineering, 55 Prospect Street, New Haven, Connecticut 06511, United States.
Brendan K
BK
Huang
Yale School of Medicine, Department of Diagnostic Radiology, P.O. Box 208043, New Haven, Connecticut 06520, United States.
Ute A
UA
Gamm
Yale School of Medicine, Department of Diagnostic Radiology, P.O. Box 208043, New Haven, Connecticut 06520, United States.
Stephan
S
Jonas
Yale School of Medicine, Department of Pediatrics, P.O. Box 208064, New Haven, Connecticut 06520, United StatesdYale School of Medicine, Department of Genetics, 333 Cedar Street, New Haven, Connecticut 06510, United States.
Mustafa K
MK
Khokha
Yale University, Department of Biomedical Engineering, 55 Prospect Street, New Haven, Connecticut 06511, United StatesbYale School of Medicine, Department of Diagnostic Radiology, P.O. Box 208043, New Haven, Connecticut 06520, United StatescYale School of.
Michael A
MA
Choma
D000818:Animals; D002923:Cilia / Q000502:physiology*; D009079:Mucociliary Clearance / Q000502:physiology*; D010641:Phenotype; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D041623:Tomography, Optical Coherence / Q000379:methods*; D014981:Xenopus
D012701:Serotonin