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16.04.18 Rawlins lab identify two genes required for regulation of multiciliated cell differentiation

last modified Apr 20, 2018 05:42 PM
In this Biology Open paper, Johnson et al. developed an in vitro explant assay of embryonic mouse trachea to test over-expression of genes from multiciliated cells
16.04.18 Rawlins lab identify two genes required for regulation of multiciliated cell differentiation

First author Dr Jo-Anne Johnson is interviewed in Biology Open.

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

Johnson J-A et al. (2018) Biol. Open 7: bio033944, DOI:10.1242/bio.033944.


Abstract from the paper

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.



An interview with the paper's first author Jo-Anne Johnson is published in the same issue of the journal. Jo-Anne is a clinical research fellow in the Rawlins lab, investigating respiratory development, multiciliogenesis and stem/progenitor cell fate determinants.



Read more about research in the Rawlins lab.

Watch Emma Rawlins describe her research on video.

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The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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