Cell cycle-related kinase is a crucial regulator for ciliogenesis and Hedgehog signaling in embryonic mouse lung development

• Published in: BMB reports Vol. 53; no. 7; pp. 367 - 372
• Main Authors: Lee, Hankyu, Ko, Hyuk Wan
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 31.07.2020; 생화학분자생물학회
• Subjects: Animals; Cell Cycle - physiology; Cell Division - physiology; Cell Proliferation - physiology; Cilia - genetics; Cilia - metabolism; Cyclin-Dependent Kinases - metabolism; Embryo, Mammalian - metabolism; Embryonic Development - physiology; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Lung - embryology; Lung - metabolism; Mice - embryology; Mice, Inbred C3H; Morphogenesis; Neural Tube - embryology; Signal Transduction - physiology; 화학
• ISSN: 1976-6696; 1976-670X; 1976-670X
• DOI: 10.5483/bmbrep.2020.53.7.295

Cell cycle-related kinase (CCRK) has a conserved role in ciliogenesis, and Ccrk defects in mice lead to developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, retinal degeneration, and polycystic kidney. Here, we found that Ccrk is highly expressed in mouse trachea and bronchioles. Ccrk mutants exhibited pulmonary hypoplasia and abnormal branching morphogenesis in respiratory organ development. Furthermore, we demonstrated that Ccrk mutant lungs exhibit not only impaired branching morphogenesis but also a significant sacculation deficiency in alveoli associated with reduced epithelial progenitor cell proliferation. In pseudoglandular stages, Ccrk mutant lungs showed a downregulation of Hedgehog (Hh) signaling and defects in cilia morphology and frequency during progenitor-cell proliferation. Interestingly, we observed that activation of the Hh signaling pathway by small-molecule smoothened agonist (SAG) partially rescued bud morphology during branch bifurcation in explants from Ccrk mutant lungs. Therefore, CCRK properly regulates respiratory airway architecture in part through Hh-signal transduction and ciliogenesis. [BMB Reports 2020; 53(7): 367-372].