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Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium.

Johnson, J-A; Watson, JK; Nikolić, MZ; Rawlins, EL; (2018) Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium. Biol Open , 7 (4) , Article bio033944. 10.1242/bio.033944. Green open access

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Abstract

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 Fibronectin type 3 and ankyrin repeat domains 1 (Fank1) and JAZF zinc finger 1 (Jazf1) 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 article has an associated First Person interview with the first author of the paper.

Type: Article
Title: Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/bio.033944
Publisher version: http://dx.doi.org/10.1242/bio.033944
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Cell fate, Cilia, Foxj1, Lung, Mcin, Notch
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10051084
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