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Foxj1 transcription factors are master regulators of the motile ciliogenic program

Abstract

Motile cilia induce fluid movement through their rhythmic beating activity. In mammals, the transcription factor Foxj1 has been implicated in motile cilia formation. Here we show that a zebrafish Foxj1 homolog, foxj1a, is a target of Hedgehog signaling in the floor plate. Loss of Foxj1a compromises the assembly of motile cilia that decorate floor plate cells. Besides the floor plate, foxj1a is expressed in Kupffer's vesicle and pronephric ducts, where it also promotes ciliary differentiation. We show that Foxj1a activates a constellation of genes essential for motile cilia formation and function, and that its activity is sufficient for ectopic development of cilia that resemble motile cilia. We also document that a paralogous gene, foxj1b, is expressed in the otic vesicle and seems to regulate motile cilia formation in this tissue. Our findings identify a dedicated master regulatory role for Foxj1 in the transcriptional program that controls the production of motile cilia.

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Figure 1: Expression pattern of zebrafish foxj1a during embryogenesis.
Figure 2: Foxj1a is essential for motile cilia formation in the floor plate, pronephric ducts and Kupffer's vesicle.
Figure 3: Foxj1a regulates the expression of dnah9 and cetn2.
Figure 4: Foxj1a activity is sufficient for the induction of motile ciliogenic gene expression.
Figure 5: Promoters of the dynein and wdr78 genes are responsive to Foxj1a activity.
Figure 6: Foxj1a associates with the promoters of the dynein and the wdr78 genes in vivo.
Figure 7: Foxj1a is sufficient for the generation of motile cilia–like cilia.
Figure 8: foxj1b is expressed in the otic vesicle, and can regulate motile ciliogenic gene expression and induce ectopic motile cilia–like cilia.

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Acknowledgements

We wish to thank J. Briscoe for discussion, M. Ma for the plasmid containing zebrafish cetn2 cDNA, C.X. Goh for technical assistance, S. Choksi for advice on ChIP and S. Choksi and other members of our laboratory for their comments on the manuscript. This work was funded by the Institute of Molecular and Cell Biology and the Agency for Science, Technology and Research of Singapore. S.R. is an adjunct faculty member in the Department of Biological Sciences, National University of Singapore.

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S.R. and X.Y. designed the study; X.Y. performed almost all of the experiments with assistance from S.R.; C.P.N. carried out the TEM analysis; H.H. contributed to the expression analysis of foxj1a. S.R. wrote the paper with constructive input from X.Y.

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Correspondence to Sudipto Roy.

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Yu, X., Ng, C., Habacher, H. et al. Foxj1 transcription factors are master regulators of the motile ciliogenic program. Nat Genet 40, 1445–1453 (2008). https://doi.org/10.1038/ng.263

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