TGF-β Signaling Regulates the Differentiation of Motile Cilia
Open accessAbstract
The cilium is a small cellular organelle with motility- and/or sensory-related functions that plays a crucial role during developmental and homeostatic processes. Although many molecules or signal transduction pathways that control cilia assembly have been reported, the mechanisms of ciliary length control have remained enigmatic. Here, we report that Smad2-dependent transforming growth factor β (TGF-β) signaling impacts the length of motile cilia at the Xenopus left-right (LR) organizer, the gastrocoel roof plate (GRP), as well as at the neural tube and the epidermis. Blocking TGF-β signaling resulted in the absence of the transition zone protein B9D1/MSKR-1 from cilia in multi-ciliated cells (MCCs) of the epidermis. Interestingly, this TGF-β activity is not mediated by Mcidas, Foxj1, and RFX2, the known major regulators of ciliogenesis. These data indicate that TGF-β signaling is crucial for the function of the transition zone, which in turn may affect the regulation of cilia length.
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Emerging evidence from mouse models and post-mortem human brains indicates changes in the morphology of primary cilia, with differences in ciliary length and abundance.
“Emerging evidence from both mouse models and post-mortem analyses of human brains indicates changes in the morphology of PC, with several studies reporting differences in ciliary length and abundance [54,55].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [55]
The Results and Discussion (pages unavailable) report shortened motile cilia in Xenopus embryos after TGF-β signaling was blocked, supporting only the general point that ciliary length can change. The paper does not report changes in primary-cilium length or abundance in mouse models or post-mortem human brains; its Results say the non-motile monocilia examined seemed unaffected. (LLM, conf=0.85)
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Cites
Normal Table of Xenopus Laevis (Daudin)
Nieuwkoop, P. D., & Faber, J. (1958) · Copeia · doi:10.2307/1439568 · Cited by 4,542 · see citing works
Appendix G: In Situ Hybridization: An Improved Whole-Mount Method for Xenopus Embryos
Harland, R. M. (1991) · Methods in cell biology · doi:10.1016/s0091-679x(08)60307-6 · Cited by 2,048 · see citing works
Hildebrandt, F., Benzing, T., & Katsanis, N. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1010172 · Cited by 1,331 · see citing works
Ciliogenesis: building the cell's antenna
Ishikawa, H., & Marshall, W. F. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3085 · Cited by 956 · see citing works
Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse
McGrath, J. M., Somlo, S., Makova, S. Z., Tian, X., & Brueckner, M. K. (2003) · Cell · doi:10.1016/s0092-8674(03)00511-7 · Cited by 797 · see citing works
Macías‐Silva, M., Abdollah, S., Hoodless, P. A., Pirone, R., Attisano, L., & Wrana, J. L. (1996) · Cell · doi:10.1016/s0092-8674(00)81817-6 · Cited by 735 · see citing works
Foxj1 transcription factors are master regulators of the motile ciliogenic program
Yu, X., Ng, C. P., Habacher, H., & Roy, S. (2008) · Nature Genetics · doi:10.1038/ng.263 · Cited by 495 · see citing works
Abnormal Nodal Flow Precedes Situs Inversus in iv and inv mice
Okada, Y., Nonaka, S., Tanaka, Y., Saijoh, Y., Hamada, H., & Hirokawa, N. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80197-5 · Cited by 428 · see citing works
Switching on cilia: transcriptional networks regulating ciliogenesis
Choksi, S. P., Lauter, G., Swoboda, P., & Roy, S. (2014) · Development · doi:10.1242/dev.074666 · Cited by 359 · see citing works
The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos
Stubbs, J. L., Oishi, I., Izpisúa Belmonte, J. C., & Kintner, C. (2008) · Nature Genetics · doi:10.1038/ng.267 · Cited by 327 · see citing works
TGF-β Signaling Is Associated with Endocytosis at the Pocket Region of the Primary Cilium
Clement, C. A., Ajbro, K., Koefoed, K., Vestergaard, M. L., Veland, I. R., de Jesus, M. P. R. H., Pedersen, L. B., Benmerah, A., Andersen, C. Y., Larsen, L. A., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.020 · Cited by 320 · see citing works
Wallingford, J. B., & Mitchell, B. J. (2011) · Genes & Development · doi:10.1101/gad.2008011 · Cited by 304 · see citing works
FGF signalling during embryo development regulates cilia length in diverse epithelia
Neugebauer, J. M., Amack, J. D., Peterson, A. G., Bisgrove, B. W., & Yost, H. J. (2009) · Nature · doi:10.1038/nature07753 · Cited by 260 · see citing works
Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation
Stubbs, J. L., Vladar, E. K., Axelrod, J. D., & Kintner, C. R. (2012) · Nature Cell Biology · doi:10.1038/ncb2406 · Cited by 241 · see citing works
Scoring a backstage pass: Mechanisms of ciliogenesis and ciliary access
García-Gonzalo, F. R., & Reiter, J. F. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201111146 · Cited by 239 · see citing works
Notch signaling regulates left–right asymmetry determination by inducingNodalexpressionPreprint
Krebs, L. T., Iwai, N., Nonaka, S., et al. (2003) · Genes & Development · doi:10.1101/gad.1084703 · Cited by 237 · 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
Raya, Á., Kawakami, Y., Rodrı́guez-Esteban, C., et al. (2003) · Genes & Development · doi:10.1101/gad.1084403 · Cited by 183 · see citing works
Xenopus laevis: Practical uses in cell and molecular biology. Solutions and protocols.
Peng, H. B. (1991) · PubMed · Cited by 176 · see citing works
Antic, D., Stubbs, J. L., Suyama, K. L., Kintner, C. R., Scott, M. P., & Axelrod, J. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008999 · Cited by 175 · see citing works
The evolution and conservation of left-right patterning mechanisms
Blum, M., Feistel, K., Thumberger, T., & Schweickert, A. (2014) · Development · doi:10.1242/dev.100560 · Cited by 172 · see citing works
Self-citationThe heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality
Boskovski, M. T., Yuan, S., Borbye‐Lorenzen, N., Goth, C. K., Makova, S. Z., Clausen, H., Brueckner, M. K., & Khokha, M. K. (2013) · Nature · doi:10.1038/nature12723 · Cited by 171 · see citing works
Transcriptional control of genes involved in ciliogenesis: a first step in making cilia
Thomas, J., Morlé, L., Soulavie, F., Laurençon, A., Sagnol, S., & Durand, B. (2010) · Biology of the Cell · doi:10.1042/bc20100035 · Cited by 170 · see citing works
Multicilin drives centriole biogenesis via E2f proteinsPreprint
Ma, L., Quigley, I. K., Omran, H., & Kintner, C. R. (2014) · Genes & Development · doi:10.1101/gad.243832.114 · Cited by 159 · see citing works
The Nodal Inhibitor Coco Is a Critical Target of Leftward Flow in Xenopus
Schweickert, A., Vick, P., Getwan, M., Weber, T., Schneider, I., Eberhardt, M., Beyer, T., Pachur, A., & Blum, M. (2010) · Current Biology · doi:10.1016/j.cub.2010.02.061 · Cited by 149 · see citing works
Self-citationCoordinated genomic control of ciliogenesis and cell movement by RFX2
Chung, M.-I., Kwon, T., Tu, F., Brooks, E., Gupta, R., Meyer, M. D., Baker, J. C., Marcotte, E. M., & Wallingford, J. B. (2014) · eLife · doi:10.7554/elife.01439 · Cited by 143 · see citing works
The transition zone: an essential functional compartment of cilia
Szymańska, K., & Johnson, C. A. (2012) · Cilia · doi:10.1186/2046-2530-1-10 · Cited by 134 · see citing works
Notch signalling regulates left-right asymmetry through ciliary length control
Lopes, S. S., Lourenço, R., Pacheco, L. G. C. A., Moreno, N., Kreiling, J. A., & Saúde, L. (2010) · Development · doi:10.1242/dev.054452 · Cited by 126 · see citing works
Hayes, J. M., Kim, S. K., Abitua, P. B., Park, T. J., Herrington, E. R., Kitayama, A., Grow, M. W., Ueno, N., & Wallingford, J. B. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.09.031 · Cited by 120 · see citing works
RFX2 is broadly required for ciliogenesis during vertebrate development
Chung, M.-I., Peyrot, S. M., LeBoeuf, S. E., Park, T. J., McGary, K. L., Marcotte, E. M., & Wallingford, J. B. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.12.029 · Cited by 116 · see citing works
Mureşan, V., Joshi, H. C., & Besharse, J. C. (1993) · Journal of Cell Science · doi:10.1242/jcs.104.4.1229 · Cited by 106 · see citing works
Vick, P., Schweickert, A., Weber, T., Eberhardt, M., Mencl, S., Shcherbakov, D., Beyer, T., & Blum, M. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.05.547 · Cited by 84 · see citing works
Self-citationWalentek, P., Beyer, T., Thumberger, T., Schweickert, A., & Blum, M. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.005 · Cited by 83 · see citing works
Self-citationThe left–right axis is regulated by the interplay of Coco, Xnr1 and derrière in Xenopus embryos
Vonica, A., & Brivanlou, A. H. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.09.039 · Cited by 80 · see citing works
Dominant-Negative Smad2 Mutants Inhibit Activin/Vg1 Signaling and Disrupt Axis Formation in Xenopus
Hoodless, P. A., Tsukazaki, T., Nishimatsu, S., Attisano, L., Wrana, J. L., & Thomsen, G. H. (1999) · Developmental Biology · doi:10.1006/dbio.1998.9168 · Cited by 76 · see citing works
Suzuki, M., Satoh, A., Ide, H., & Tamura, K. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.01.019 · Cited by 73 · see citing works
Chung, M.-I., Nascone‐Yoder, N. M., Grover, S. A., Drysdale, T. A., & Wallingford, J. B. (2010) · Development · doi:10.1242/dev.044610 · Cited by 71 · see citing works
Ciliogenesis and cerebrospinal fluid flow in the developing Xenopus brain are regulated by foxj1
Hagenlocher, C., Walentek, P., Müller, C., Thumberger, T., & Feistel, K. (2013) · Cilia · doi:10.1186/2046-2530-2-12 · Cited by 70 · see citing works
Qiu, D., Cheng, S., Wozniak, L., et al. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20509 · Cited by 69 · see citing works
Sakano, D., Kato, A., Parikh, N., McKnight, K., Terry, D. E., Stefanovic, B., & Kato, Y. (2010) · Developmental Cell · doi:10.1016/j.devcel.2009.12.023 · Cited by 57 · see citing works
Self-citationPAR1 specifies ciliated cells in vertebrate ectoderm downstream of aPKC
Ossipova, O., Tabler, J., Green, J. B. A., & Sokol, S. Y. (2007) · Development · doi:10.1242/dev.009282 · Cited by 49 · see citing works
Whole-Mount Fluorescence Immunocytochemistry on Xenopus EmbryosPreprint
Lee, C., Kieserman, E. K., Gray, R. S., et al. (2008) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot4957 · Cited by 48 · see citing works
RFX7 is required for the formation of cilia in the neural tube
Manojlovic, Z., Earwood, R., Kato, A., Stefanovic, B., & Kato, Y. (2014) · Mechanisms of Development · doi:10.1016/j.mod.2014.02.001 · Cited by 46 · see citing works
Self-citationThe POU homeobox protein Oct-1 regulates radial glia formation downstream of Notch signaling
Kiyota, T., Kato, A., Altmann, C. R., et al. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2007.12.013 · Cited by 42 · see citing works
Self-citationBecker, B. E., & Gard, D. L. (2006) · Methods in molecular biology · doi:10.1007/978-1-59745-000-3_6 · Cited by 38 · see citing works
Chen, Y., Mironova, E. S., Whitaker, L. L., Edwards, L., Yost, H. J., & Ramsdell, A. F. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2003.12.035 · Cited by 36 · see citing works
Takada, H., Hattori, D., Kitayama, A., Ueno, N., & Taira, M. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.04.020 · Cited by 29 · see citing works
The multiple roles of Notch signaling during left-right patterning
Kato, Y. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0695-5 · Cited by 28 · see citing works
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Christensen, S. T., Morthorst, S. K., Mogensen, J. B., & Pedersen, L. B. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028167 · Cited by 125 · see citing works
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“Emerging evidence from both mouse models and post-mortem analyses of human brains indicates changes in the morphology of PC, with several studies reporting differences in ciliary length and abundance [54,55].”
- Authors
- Tözser, J., Earwood, R., Kato, A., Brown, J., Tanaka, K., Didier, R., Megraw, T. L., Blum, M., & Kato, Y.
- Affiliations
- University of Hohenheim (DE)
- Florida State University (US)
- Corresponding author
- Blum, Martin
- Kato, Yoichi
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 11
- Issue
- 7
- Pages
- 1000-1007
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4439334
- OpenAlex
- W1565308349
- Cited by
- 30
- References
- 48
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 2
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of General Medical Sciences (GM087641, R15GM087641)
- 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 › TGF-β signaling in diseases
- Keywords
- TGF-beta signaling, motile cilia, Smad2, ciliogenesis, transition zone, left-right organizer, neural tube, epidermis, Xenopus
- MeSH terms
- Animals, Cilia, Immunohistochemistry, Xenopus, Signal Transduction, Transforming Growth Factor beta, Microscopy, Confocal, Smad2 Protein
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