A secretory cell type develops alongside multiciliated cells, ionocytes and goblet cells, and provides a protective, anti-infective function in the frog embryonic mucociliary epidermis
Open accessAbstract
The larval epidermis of Xenopus is a bilayered epithelium, which is an excellent model system for the study of the development and function of mucosal and mucociliary epithelia. Goblet cells develop in the outer layer while multiciliated cells and ionocytes sequentially intercalate from the inner to the outer layer. Here, we identify and characterise a fourth cell type, the small secretory cell (SSC). We show that the development of these cells is controlled by the transcription factor Foxa1 and that they intercalate into the outer layer of the epidermis relatively late, at the same time as embryonic hatching. Ultrastructural and molecular characterisation shows that these cells have an abundance of large apical secretory vesicles, which contain highly glycosylated material, positive for binding of the lectin, peanut agglutinin, and an antibody to the carbohydrate epitope, HNK-1. By specifically depleting SSCs, we show that these cells are crucial for protecting the embryo against bacterial infection. Mass spectrometry studies show that SSCs secrete a glycoprotein similar to Otogelin, which may form the structural component of a mucus-like protective layer, over the surface of the embryo, and several potential antimicrobial substances. Our study completes the characterisation of all the epidermal cell types in the early tadpole epidermis and reinforces the suitability of this system for the in vivo study of complex epithelia, including investigation of innate immune defences.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
foxA specifies small 5HT-secreting cells in the mucociliary epithelium that regulate ciliary beating.
“moreover, foxA has been found to specify small 5HT-secreting cells in the mucociliary epithelium that regulate ciliary beating [117,118].”
From Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution (2015) · cites this paper as [117]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Zasloff, M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.15.5449 · Cited by 2,305 · 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
Complement and its role in innate and adaptive immune responses
Dunkelberger, J. R., & Song, W.-C. (2010) · Cell Research · doi:10.1038/cr.2009.139 · Cited by 1,932 · see citing works
Structure and Function of the Polymeric Mucins in Airways Mucus
Thornton, D. J., Rousseau, K., & McGuckin, M. A. (2007) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100702 · Cited by 824 · see citing works
Self-citationThe Genome of the Western Clawed Frog Xenopus tropicalis
Hellsten, U., Harland, R. M., Gilchrist, M. J., Hendrix, D. A., Jurka, J., Kapitonov, V., Ovcharenko, I., Putnam, N. H., Shu, S., Taher, L., et al. (2010) · Science · doi:10.1126/science.1183670 · Cited by 798 · see citing works
Self-citationSubmucosal glands are the predominant site of CFTR expression in the human bronchus
Engelhardt, J. F., Yankaskas, J. R., Ernst, S. A., Yang, Y., Marino, C. R., Boucher, R. C., Cohn, J. A., & Wilson, J. M. (1992) · Nature Genetics · doi:10.1038/ng1192-240 · Cited by 654 · see citing works
Structures of complement component C3 provide insights into the function and evolution of immunity
Janssen, B. J. C., Huizinga, E. G., Raaijmakers, H. C. A., Roos, A., Daha, M. R., Nilsson‐Ekdahl, K., Nilsson, B., & Gros, P. (2005) · Nature · doi:10.1038/nature04005 · Cited by 542 · 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
Park, T. J., Mitchell, B. J., Abitua, P. B., Kintner, C. R., & Wallingford, J. B. (2008) · Nature Genetics · doi:10.1038/ng.104 · Cited by 448 · see citing works
Regulation of mucociliary clearance in health and disease
Houtmeyers, E., Gosselink, R., Gayan‐Ramirez, G., & Decramer, M. (1999) · European Respiratory Journal · doi:10.1034/j.1399-3003.1999.13e39.x · Cited by 421 · see citing works
Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis
Kim, S. K., Shindo, A., Park, T. J., Oh, E. C. T., Ghosh, S., Gray, R. S., Lewis, R. A., Johnson, C. A., Attié‐Bitach, T., Katsanis, N., et al. (2010) · Science · doi:10.1126/science.1191184 · Cited by 348 · 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
Gel-forming mucins appeared early in metazoan evolution
Lang, T., Hansson, G. C., & Samuelsson, T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705984104 · Cited by 317 · see citing works
Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1
Robinson, J. L. L., MacArthur, S., Ross-Innes, C. S., Tilley, W. D., Neal, D. E., Mills, I. G., & Carroll, J. S. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.216 · Cited by 300 · see citing works
Garcia, M. A. S., Yang, N., & Quinton, P. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38662 · Cited by 289 · see citing works
A positive feedback mechanism governs the polarity and motion of motile cilia
Mitchell, B. J., Jacobs, R., Li, J., Chien, S., & Kintner, C. R. (2007) · Nature · doi:10.1038/nature05771 · Cited by 285 · 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
Johansson, M., Thomsson, K. A., & Hansson, G. C. (2009) · Journal of Proteome Research · doi:10.1021/pr9002504 · Cited by 237 · see citing works
Programmed Cell Death duringXenopusDevelopment: A Spatio-temporal Analysis
Hensey, C. E., & Gautier, J. (1998) · Developmental Biology · doi:10.1006/dbio.1998.9028 · Cited by 236 · see citing works
Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues.
Besnard, V., Wert, S., Hull, W., & Whitsett, J. (2004) · Gene Expression Patterns · doi:10.1016/j.modgep.2004.08.006 · Cited by 227 · see citing works
Kim, S., Yamamoto, A., Bouwmeester, T., Agius, E., & Robertis, E. M. D. (1998) · Development · doi:10.1242/dev.125.23.4681 · Cited by 220 · see citing works
Antimicrobial properties of peptides from Xenopus granular gland secretions
Soravia, E., Martini, G., & ZASLOFF, M. A. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)80027-9 · Cited by 217 · see citing works
Deblandre, G. A., Wettstein, D. A., Koyano‐Nakagawa, N., & Kintner, C. R. (1999) · Development · doi:10.1242/dev.126.21.4715 · Cited by 199 · see citing works
Simons, M., Gault, W. J., Gotthardt, D. N., Rohatgi, R., Klein, T. J., Shao, Y., Lee, H., Wu, A.-L., Fang, Y., Satlin, L. M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1836 · Cited by 178 · see citing works
Vitellogenin Functions as a Multivalent Pattern Recognition Receptor with an Opsonic Activity
Li, Z., Zhang, S., & Liu, Q. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001940 · Cited by 173 · see citing works
Foxa1 and Foxa2 Control the Differentiation of Goblet and Enteroendocrine L- and D-Cells in Mice
Ye, D. Z., & Kaestner, K. H. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.08.059 · Cited by 168 · see citing works
Apolipoprotein B Is an Innate Barrier against Invasive Staphylococcus aureus Infection
Peterson, M. M., Mack, J. L., Hall, P. R., Alsup, A. A., Alexander, S. M., Sully, E. K., Sawires, Y. S., Cheung, A. L., Otto, M. J., & Gresham, H. D. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.10.001 · Cited by 157 · see citing works
Vitellogenin, a multivalent sensor and an antimicrobial effector
Zhang, S., Wang, S., Li, H., et al. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.11.003 · Cited by 156 · see citing works
Thornton, D. J., Khan, N., Mehrotra, R., et al. (1999) · Glycobiology · doi:10.1093/glycob/9.3.293 · Cited by 153 · see citing works
Self-citationOtogelin: A glycoprotein specific to the acellular membranes of the inner ear
Cohen‐Salmon, M., El-Amraoui, A., Leibovici, M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14450 · Cited by 148 · see citing works
Unpacking a gel-forming mucin: a view of MUC5B organization after granular release
Kesımer, M., Makhov, A. M., Griffith, J. D., et al. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00194.2009 · Cited by 141 · see citing works
Vitellogenin is a novel player in defense reactions
Shi, X., Zhang, S., & PANG, Q. (2005) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2005.09.005 · Cited by 138 · 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
Specification of ion transport cells in theXenopuslarval skin
Quigley, I. K., Stubbs, J. L., & Kintner, C. R. (2011) · Development · doi:10.1242/dev.055699 · Cited by 120 · see citing works
Defining a large set of full-length clones from a Xenopus tropicalis EST project
Gilchrist, M. J., Zorn, A. M., Voigt, J., et al. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.04.023 · Cited by 114 · see citing works
Foxa1 and Foxa2 Maintain the Metabolic and Secretory Features of the Mature β-Cell
Gao, N., Lay, J. E. L., Qin, W. D., Doliba, N. M., Schug, J., Fox, A. J., Smirnova, O., Matschinsky, F. M., & Kaestner, K. H. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0513 · Cited by 110 · see citing works
Dubaissi, E., & Papalopulu, N. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.006494 · Cited by 102 · see citing works
Self-citationAlbert, T., Laubinger, W., Müller, S., et al. (2010) · Journal of Proteome Research · doi:10.1021/pr100020c · Cited by 99 · see citing works
Schraders, M., Ruiz-Palmero, L., Kalay, E., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.09.012 · Cited by 96 · see citing works
The mechanism and pattern of yolk consumption provide insight into embryonic nutrition in Xenopus
Jorgensen, P., Steen, J. A. J., Steen, H., et al. (2009) · Development · doi:10.1242/dev.032425 · Cited by 87 · see citing works
FOXA1 Is a Potential Oncogene in Anaplastic Thyroid Carcinoma
Nucera, C., Eeckhoute, J., Finn, S. P., Carroll, J. S., Ligon, A. H., Priolo, C., Fadda, G., Toner, M. E., Sheils, O. M., Attard, M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-3155 · Cited by 80 · see citing works
Methods for Separation and Deglycosylation of Mucin Subunits
Thornton, D. J., Howard, M., Devine, P. L., et al. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1266 · Cited by 77 · see citing works
Self-citationVitellogenin is an acute phase protein with bacterial-binding and inhibiting activities
Tong, Z., Li, L., Pawar, R., & Zhang, S. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.10.001 · Cited by 70 · see citing works
Meucci, V., & Arukwe, A. (2005) · Aquatic Toxicology · doi:10.1016/j.aquatox.2005.03.021 · Cited by 68 · see citing works
FoxA1 as a lineage-specific oncogene in luminal type breast cancer
Yamaguchi, N., Ito, E., Azuma, S., Honma, R., Yanagisawa, Y., Nishikawa, A., Kawamura, M., Imai, J., Tatsuta, K., Inoue, J., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.11.064 · Cited by 63 · see citing works
van der Sluis, M., Vincent, A., Bouma, J., Male, A. K. K.-V., van Goudoever, J., Renes, I., & van Seuningen, I. (2008) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2008.02.158 · Cited by 61 · see citing works
Walentek, 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
Self-citationDrysdale, T. A., & Elinson, R. P. (1992) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.1992.00051.x · Cited by 60 · see citing works
Slack, J. M. W. (1985) · Cell · doi:10.1016/0092-8674(85)90077-7 · Cited by 60 · see citing works
Functional and molecular characterization of an anion exchanger in airway serous epithelial cells
Loffing, J., Moyer, B. D., Reynolds, D., et al. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.4.c1016 · Cited by 60 · see citing works
Fine structural changes in the differentiating epidermis of Xenopus laevis embryos.
Billett, F. S., & Gould, R. P. (1971) · PubMed · Cited by 53 · see citing works
Jonckheere, N., Vincent, A., Perrais, M., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700905200 · Cited by 51 · see citing works
Hauser, F., & Hoffmann, W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35809-5 · Cited by 50 · see citing works
Soto, X., Li, J., Lea, R., Dubaissi, E., Papalopulu, N., & Amaya, E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217308110 · Cited by 37 · see citing works
Self-citationSchumacher, U., Adam, E. C., Hauser, F., et al. (1994) · Journal of Histochemistry & Cytochemistry · doi:10.1177/42.1.7903329 · Cited by 30 · see citing works
Nagata, S., Nakanishi, M., Nanba, R., et al. (2003) · Development Genes and Evolution · doi:10.1007/s00427-003-0341-9 · Cited by 26 · see citing works
Multicolor Fluorescent In Situ mRNA Hybridization (FISH) on Whole Mounts and Sections
Lea, R., Bonev, B., Dubaissi, E., Vize, P. D., & Papalopulu, N. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-992-1_24 · Cited by 23 · see citing works
Self-citationZASLOFF, M. A. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2009.04.011 · Cited by 18 · see citing works
Cohen‐Salmon, M., Mattéi, M., & Petit, C. (1999) · Mammalian Genome · doi:10.1007/s003359901033 · Cited by 17 · see citing works
Montorzi, M., Burgos, M. H., & Falchuk, K. H. (2000) · Molecular Reproduction and Development · doi:10.1002/(sici)1098-2795(200001)55:1 · Cited by 14 · see citing works
Alteration of ocular surface mucins in MUC5AC-DTA transgenic mice.
Wang, I., Yu, C., & Hu, F. (2009) · PubMed · Cited by 11 · see citing works
Somasekhar, T., & Nordlander, R. H. (1997) · Developmental Brain Research · doi:10.1016/s0165-3806(97)00011-4 · Cited by 9 · see citing works
Antibody Development and Use in Chromogenic and Fluorescent Immunostaining
Dubaissi, E., Panagiotaki, N., Papalopulu, N., & Vize, P. D. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-992-1_23 · Cited by 8 · see citing works
Self-citationSecretion of chondroitin sulfate from embryonic epidermal cells in Xenopus laevis.
Nishikawa, S., & Sasaki, F. (1993) · Journal of Histochemistry & Cytochemistry · doi:10.1177/41.9.8354877 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Walentek, 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
Self-citation
- Authors
- Dubaissi, E., Rousseau, K., Lea, R., Soto, X., Nardeosingh, S., Schweickert, A., Amaya, E., Thornton, D. J., & Papalopulu, N.
- Affiliations
- University of Manchester (GB)
- Wellcome Centre for Cell-Matrix Research (GB)
- University of Hohenheim (DE)
- Corresponding author
- Papalopulu, Nancy
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2014-04-01
- Volume
- 141
- Issue
- 7
- Pages
- 1514-1525
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC3957375
- OpenAlex
- W2127084153
- Cited by
- 81
- References
- 64
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 13 · 2020: 12 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 2 · 2015: 9 · 2014: 4
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Development (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust (WT 088785/Z/09/Z, WT 090868Z/09/Z, 090868, 088785/Z/09/Z, 097820/Z/11/Z, 097820, 088785/Z/09)
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Urology › Comparative Animal Anatomy Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- mucociliary epithelium, Xenopus tadpoles, epidermal cell types, FOXA1, cell intercalation, HNK-1, antimicrobial peptides, innate immunity, bacterial infection resistance, embryonic hatching, epithelial development
- MeSH terms
- Animals, Cell Differentiation, Cilia, Embryo, Nonmammalian, Epidermis, Glycoproteins, Immunity, Innate, Ions, Larva, Mucus, Xenopus, Goblet Cells, Secretory Vesicles, Hepatocyte Nuclear Factor 3-alpha, Secretory Pathway
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
