Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium
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Johnson, J., Watson, J. K., Nikolic, M., & Rawlins, E. L. Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium. Biology Open, 7 (bio033944)https://doi.org/10.1242/bio.033944
The airways are lined by secretory and multiciliated cells which function together to remove particles and debris from the respiratory tract. The transcriptome of multiciliated cells has been extensively studied, but the function of many of the genes identified is unknown. We have established an assay to test the ability of over-expressed transcripts to promote multiciliated cell differentiation in mouse embryonic tracheal explants. Overexpression data indicated that Fank1 (Fibronectin type 3 and ankyrin repeat domains 1) and Jazf1 (JAZF zinc finger 1) promoted multiciliated cell differentiation alone, and cooperatively with the canonical multiciliated cell transcription factor Foxj1. Moreover, knock-down of Fank1 or Jazf1 in adult mouse airway epithelial cultures demonstrated that these factors are both required for ciliated cell differentiation in vitro. This analysis identifies Fank1 and Jazf1 as novel regulators of multiciliated cell differentiation. Moreover, we show that they are likely to function downstream of IL6 signalling and upstream of Foxj1 activity in the process of ciliated cell differentiation. In addition, our in vitro explant assay provides a convenient method for preliminary investigation of over-expression phenotypes in the developing mouse airways.
This study was supported by the Medical Research Council (G0900424 and MR/P009581/1 to E.L.R.), the Wellcome Trust (Clinical PhD Fellowship to J.-A.J.; 092087), the Seventh Framework Programme (200720; FP7/2008 to E.L.R.), the Isaac Newton Trust (to E.L.R.) and Gurdon Institute core funding from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492).
External DOI: https://doi.org/10.1242/bio.033944
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275893
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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