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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The evolutionary divergence of mucociliary cell types in metazoans appears closely linked to the diversification of the Fox gene family.
“At the molecular level, the evolutionary divergence of mucociliary cell types in metazoans appears to be closely linked to the diversification of the Fox gene family.”
From Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution (2015) · cites this paper as [113]
Cites
The Primary Cilium as the Cell's Antenna: Signaling at a Sensory Organelle
Singla, V., & Reiter, J. F. (2006) · Science · doi:10.1126/science.1124534 · Cited by 1,179 · see citing works
Overview of Structure and Function of Mammalian Cilia
Satir, P., & Christensen, S. T. (2007) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.040705.141236 · Cited by 1,142 · cited 1× · see citing works
“In vertebrates, cilia are broadly classified as sensory and motil”
BackgroundKramer-Zucker, A. G., Olale, F., Haycraft, C. J., Yoder, B. K., Schier, A. F., & Drummond, I. A. S. (2005) · Development · doi:10.1242/dev.01772 · Cited by 671 · see citing works
Essner, J. J., Amack, J. D., Nyholm, M. K., Harris, E. B., & Yost, H. J. (2005) · Development · doi:10.1242/dev.01663 · Cited by 620 · see citing works
Nodal Flow and the Generation of Left-Right Asymmetry
Hirokawa, N., Tanaka, Y., Okada, Y., & Takeda, S. (2006) · Cell · doi:10.1016/j.cell.2006.03.002 · Cited by 576 · see citing works
Mutation of an axonemal dynein affects left–right asymmetry in inversus viscerum mice
Supp, D. M., Witte, D. P., Potter, S. S., & Brueckner, M. K. (1997) · Nature · doi:10.1038/40140 · Cited by 553 · see citing works
Chen, J., Knowles, H. J., Hebert, J. L., & Hackett, B. P. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4786 · Cited by 405 · see citing works
Use of Chromatin Immunoprecipitation To Clone Novel E2F Target Promoters
Weinmann, A. S., Bartley, S. M., Zhang, T., Zhang, M. Q., & Farnham, P. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.6820-6832.2001 · Cited by 384 · see citing works
Conserved function for embryonic nodal cilia
Essner, J. J., Vogan, K. J., Wagner, M. K., Tabin, C. J., Yost, H. J., & Brueckner, M. K. (2002) · Nature · doi:10.1038/418037a · Cited by 375 · see citing works
Karlen, S. J., Ahmad, N., & Rebagliati, M. R. (2003) · Development · doi:10.1242/dev.00436 · Cited by 368 · see citing works
Ciliogenesis and Left–Right Axis Defects in Forkhead Factor HFH-4–Null Mice
Brody, S. L., Yan, X. H., Wuerffel, M. K., Song, S., & Shapiro, S. D. (2000) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.23.1.4070 · Cited by 359 · see citing works
Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo.Preprint
Hammerschmidt, M., Bitgood, M. J., & McMahon, A. (1996) · Genes & Development · doi:10.1101/gad.10.6.647 · Cited by 352 · see citing works
The RFX-Type Transcription Factor DAF-19 Regulates Sensory Neuron Cilium Formation in C. elegans
Swoboda, P., Adler, H. T., & Thomas, J. H. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80436-0 · Cited by 336 · see citing works
Genetic Defects in Ciliary Structure and Function
Zariwala, M. A., Knowles, M. R., & Omran, H. (2006) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.040705.141301 · Cited by 313 · see citing works
A molecular pathway leading to endoderm formation in zebrafish
Alexander, J. S., & Stainier, D. Y. R. (1999) · Current Biology · doi:10.1016/s0960-9822(00)80016-0 · Cited by 303 · see citing works
Concordet, J., Lewis, K. E., Moore, J. W., Goodrich, L. V., Johnson, R. L., Scott, M. P., & Ingham, P. W. (1996) · Development · doi:10.1242/dev.122.9.2835 · Cited by 295 · see citing works
Gherman, A., Davis, E. E., & Katsanis, N. (2006) · Nature Genetics · doi:10.1038/ng0906-961 · Cited by 291 · see citing works
Zebrafishsmoothenedfunctions in ventral neural tube specification and axon tract formation
Varga, Z. M., Amores, A., Lewis, K. E., Yan, Y., Postlethwait, J. H., Eisen, J. S., & Westerfield, M. (2001) · Development · doi:10.1242/dev.128.18.3497 · Cited by 290 · see citing works
Wolff, C., Roy, S., & Ingham, P. W. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00461-5 · Cited by 276 · see citing works
Self-citationKawakami, Y., Raya, Á., Raya, R. M., Rodrı́guez-Esteban, C., & Belmonte, J. C. I. (2005) · Nature · doi:10.1038/nature03512 · Cited by 271 · see citing works
Chen, W., Burgess, S. M., & Hopkins, N. H. (2001) · Development · doi:10.1242/dev.128.12.2385 · Cited by 266 · see citing works
Liu, Y., Pathak, N. H., Kramer-Zucker, A. G., & Drummond, I. A. S. (2007) · Development · doi:10.1242/dev.02806 · Cited by 229 · see citing works
Flagellar assembly in two hundred and fifty easy-to-follow steps
Dutcher, S. K. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89123-4 · Cited by 212 · see citing works
Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells
You, Y., Huang, T., Richer, E. J., Schmidt, J.-E. H., Zabner, J., Borok, Z., & Brody, S. L. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00170.2003 · Cited by 212 · see citing works
Bonnafé, E., Touka, M., Ait‐Lounis, A., Baas, D., Barras, E., Ucla, C., Moreau, A., Flamant, F., Dubruille, R., Couble, P., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.10.4417-4427.2004 · Cited by 211 · see citing works
RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1
Pan, J., You, Y., Huang, T., & Brody, S. L. (2007) · Journal of Cell Science · doi:10.1242/jcs.005306 · Cited by 203 · see citing works
Forkhead Transcription Factor HFH-4 Expression Is Temporally Related to Ciliogenesis
Blatt, E. N., Yan, X. H., Wuerffel, M. K., Hamilos, D. L., & Brody, S. L. (1999) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.21.2.3691 · Cited by 160 · see citing works
Drosophila Regulatory factor X is necessary for ciliated sensory neuron differentiation
Dubruille, R., Laurençon, A., Vandaele, C., Shishido, E., Coulon-Bublex, M., Swoboda, P., Couble, P., Kernan, M. J., & Durand, B. (2002) · Development · doi:10.1242/dev.00148 · Cited by 158 · see citing works
Majumdar, Å., Lun, K., Brand, M., & Drummond, I. A. S. (2000) · Development · doi:10.1242/dev.127.10.2089 · Cited by 155 · see citing works
Riley, B. B., Zhu, C., Janetopoulos, C., & Aufderheide, K. J. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8736 · Cited by 149 · see citing works
Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells
Gomperts, B. N., Gong-Cooper, X., & Hackett, B. P. (2004) · Journal of Cell Science · doi:10.1242/jcs.00978 · Cited by 144 · see citing works
Jagged2a-Notch Signaling Mediates Cell Fate Choice in the Zebrafish Pronephric Duct
Ma, M., & Jiang, Y. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030018 · Cited by 134 · see citing works
Hackett, B. P., Brody, S. L., Liang, M., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4249 · Cited by 124 · see citing works
Basal body/centriole assembly and continuity
Beisson, J., & Wright, M. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00017-0 · Cited by 123 · see citing works
Two distinct cell populations in the floor plate of the zebrafish are induced by different pathways.
Odenthal, J., van Eeden, F. V., Haffter, P., Ingham, P., & Nüsslein-Volhard, C. (2000) · Developmental Biology · doi:10.1006/dbio.1999.9589 · Cited by 120 · see citing works
Lim, L., Zhou, H.-P., & Costa, R. H. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.7.3094 · Cited by 101 · see citing works
Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas
Ait‐Lounis, A., Baas, D., Barras, E., Benadiba, C., Charollais, A., Nlend, R. N., Liègeois, D., Meda, P., Durand, B., & Reith, W. (2007) · Diabetes · doi:10.2337/db06-1187 · Cited by 99 · see citing works
Foxj1 is required for apical localization of ezrin in airway epithelial cells
Huang, T., You, Y., Spoor, M. S., Richer, E. J., Kudva, V. V., Paige, R. C., Seiler, M. P., Liebler, J. M., Zabner, J., Plopper, C. G., et al. (2003) · Journal of Cell Science · doi:10.1242/jcs.00830 · Cited by 94 · see citing works
Cooperation of sonic hedgehog enhancers in midline expression
Ertzer, R., Müller, F., Hadzhiev, Y., Rathnam, S., Fischer, N., Rastegar, S., & Strähle, U. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.11.004 · Cited by 82 · see citing works
Ikeda, T., Ikeda, K., Enomoto, M., et al. (2005) · FEBS Letters · doi:10.1016/j.febslet.2004.12.070 · Cited by 62 · see citing works
Xu, J., Srinivas, B. P., Tay, S. Y., Mak, A., Yu, X., Lee, S. G. P., Yang, H. H., Govindarajan, K. R., Leong, B., Bourque, G., et al. (2006) · Genetics · doi:10.1534/genetics.106.061523 · Cited by 45 · see citing works
Self-citationPelletier, G. J., Brody, S. L., Liapis, H., et al. (1998) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1998.274.3.l351 · Cited by 37 · see citing works
Developmental expression of FoxJ1.2, FoxJ2, and FoxQ1 in Xenopus tropicalis
Choi, V. M., Harland, R. M., & Khokha, M. K. (2006) · Gene Expression Patterns · doi:10.1016/j.modgep.2005.11.007 · Cited by 27 · see citing works
Amos, W. B., Amos, L., & Linck, R. W. (1985) · Cell Motility · doi:10.1002/cm.970050306 · Cited by 16 · see citing works
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Molecular Architecture of the Mouse Nervous System
Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L. E., La Manno, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.021 · Cited by 2,995 · see citing works
Chua, R. L., Lukassen, S., Trump, S., Hennig, B. P., Wendisch, D., Pott, F., Debnath, O., Thürmann, L., Kurth, F., Völker, M. T., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0602-4 · Cited by 1,035 · see citing works
Genetics and biology of primary ciliary dyskinesia
Horani, A., Ferkol, T. W., Dutcher, S. K., & Brody, S. L. (2016) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2015.09.001 · Cited by 197 · see citing works
Motile cilia and airway disease
Legendre, M., Zaragosi, L.-E., & Mitchison, H. M. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.11.007 · Cited by 175 · see citing works
FOXM1 drives proximal tubule proliferation during repair from acute ischemic kidney injury
Chang-Panesso, M., Kadyrov, F. F., Lalli, M., Wu, H., Ikeda, S., Kefaloyianni, E., Abdelmageed, M. M., Herrlich, A., Kobayashi, A., & Humphreys, B. D. (2019) · Journal of Clinical Investigation · doi:10.1172/jci125519 · Cited by 158 · see citing works
Multiciliated Cells in Animals
Meunier, A., & Azimzadeh, J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028233 · Cited by 117 · see citing works
Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution
Arendt, D., Benito-Gutierrez, E., Brunet, T., & Marlow, H. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0286 · Cited by 112 · see citing works
Impairment of cilia architecture and ciliogenesis in hyperplastic nasal epithelium from nasal polyps
Li, Y. Y., Li, C. W., Chao, S. S., Yu, F. G., Yu, X. M., Liu, J., Yan, Y., Shen, L., Gordon, W., Shi, L., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.07.038 · Cited by 104 · see citing works
Self-citationDubaissi, E., Rousseau, K., Lea, R., Soto, X., Nardeosingh, S., Schweickert, A., Amaya, E., Thornton, D. J., & Papalopulu, N. (2014) · Development · doi:10.1242/dev.102426 · Cited by 81 · see citing works
HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus
Diggle, C. P., Moore, D. J., Mali, G., zur Lage, P., Ait-Lounis, A., Schmidts, M., Shoemark, A., Garcia Munoz, A., Halachev, M. R., Gautier, P., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004577 · Cited by 67 · see citing works
Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes
Ignatenko, O., Malinen, S., Rybas, S., Vihinen, H., Nikkanen, J., Kononov, A., Jokitalo, E. S., Ince-Dunn, G., & Suomalainen, A. (2023) · Journal of Cell Biology · doi:10.1083/jcb.202203019 · Cited by 63 · see citing works
Vij, S., Rink, J. C., Ho, H. K., Babu, D., Eitel, M., Narasimhan, V., Tiku, V., Westbrook, J., Schierwater, B., & Roy, S. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003019 · Cited by 65 · see citing works
Self-citationWalentek, P., Bogusch, S., Thumberger, T., Vick, P., Dubaissi, E., Beyer, T., Blum, M., & Schweickert, A. (2014) · Development · doi:10.1242/dev.102343 · Cited by 61 · see citing works
Ryan, R., Failler, M., Reilly, M. L., Garfa-Traore, M., Delous, M., Filhol, E., Reboul, T., Bole-Feysot, C., Nitschké, P., Baudouin, V., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddx396 · Cited by 48 · see citing works
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Tözser, J., Earwood, R., Kato, A., Brown, J., Tanaka, K., Didier, R., Megraw, T. L., Blum, M., & Kato, Y. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.025 · Cited by 30 · see citing works
- Authors
- Yu, X., Ng, C. P., Habacher, H., & Roy, S.
- Affiliations
- Institute of Molecular and Cell Biology (SG)
- National University of Singapore (SG)
- Corresponding author
- Roy, Sudipto
- Venue
- Nature Genetics
- Published
- 2008-11-16
- Volume
- 40
- Issue
- 12
- Pages
- 1445-1453
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2036582717
- Cited by
- 495
- References
- 44
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 51 · 2023: 46 · 2022: 27 · 2021: 31 · 2020: 30 · 2019: 25 · 2018: 30 · 2017: 24 · 2016: 21 · 2015: 28 · 2014: 28 · 2013: 29 · 2012: 18
- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Directorate for Biological Sciences
- Institute of Molecular and Cell Biology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- Foxj1, motile cilia, ciliogenesis, Hedgehog signaling, floor plate, Kupffer's vesicle, pronephric duct, otic vesicle, transcriptional regulation, zebrafish, ciliary beating
- MeSH terms
- Animals, Cilia, Molecular Sequence Data, Zebrafish, Signal Transduction, Zebrafish Proteins, Forkhead Transcription Factors, Hedgehog Proteins
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