Molecules and Cells

  • 제46권12호
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  • Pages.746-756
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  • 2023
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Deup1 Expression Interferes with Multiciliated Differentiation

  • Miram Shin (Department of Biological Sciences, Sookmyung Women's University) ;
  • Jiyeon Lee (Department of Biological Sciences, Sookmyung Women's University) ;
  • Haeryung Lee (Department of Biological Sciences, Sookmyung Women's University) ;
  • Vijay Kumar (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Jaebong Kim (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Soochul Park (Department of Biological Sciences, Sookmyung Women's University)
  • 투고 : 2023.09.12
  • 심사 : 2023.10.18
  • 발행 : 2023.12.31
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초록

A recent study revealed that the loss of Deup1 expression does not affect either centriole amplification or multicilia formation. Therefore, the deuterosome per se is not a platform for amplification of centrioles. In this study, we examine whether gain-of-function of Deup1 affects the development of multiciliated ependymal cells. Our time-lapse study reveals that deuterosomes with an average diameter of 300 nm have two different fates during ependymal differentiation. In the first instance, deuterosomes are scattered and gradually disappear as cells become multiciliated. In the second instance, deuterosomes self-organize into a larger aggregate, called a deuterosome cluster (DC). Unlike scattered deuterosomes, DCs possess centriole components primarily within their large structure. A characteristic of DC-containing cells is that they tend to become primary ciliated rather than multiciliated. Our in utero electroporation study shows that DCs in ependymal tissue are mostly observed at early postnatal stages, but are scarce at late postnatal stages, suggesting the presence of DC antagonists within the differentiating cells. Importantly, from our bead flow assay, ectopic expression of Deup1 significantly impairs cerebrospinal fluid flow. Furthermore, we show that expression of mouse Deup1 in Xenopus embryos has an inhibitory effect on differentiation of multiciliated cells in the epidermis. Taken together, we conclude that the DC formation of Deup1 in multiciliated cells inhibits production of multiple centrioles.

키워드

과제정보

This work was supported by grants NRF-2021R1A4A1027355, NRF-2021R1A2C3011919, and NRF-2021R1C1C2009319 from the National Research Foundation of Korea (NRF).

참고문헌

  1. Al Jord, A., Lemaitre, A., Delgehyr, N., Faucourt, M., Spassky, N., and Meunier, A. (2014). Centriole amplification by mother and daughter centrioles differs in multiciliated cells. Nature 516, 104-107. https://doi.org/10.1038/nature13770
  2. Anderson, R.G. and Brenner, R.M. (1971). The formation of basal bodies (centrioles) in the rhesus monkey oviduct. J. Cell Biol. 50, 10-34. https://doi.org/10.1083/jcb.50.1.10
  3. Banizs, B., Pike, M.M., Millican, C.L., Ferguson, W.B., Komlosi, P., Sheetz, J., Bell, P.D., Schwiebert, E.M., and Yoder, B.K. (2005). Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 132, 5329-5339. https://doi.org/10.1242/dev.02153
  4. Bienz, M. (2005). β-Catenin: a pivot between cell adhesion and Wnt signalling. Curr. Biol. 15, R64-R67. https://doi.org/10.1016/j.cub.2004.12.058
  5. Breslow, D.K. and Holland, A.J. (2019). Mechanism and regulation of centriole and cilium biogenesis. Annu. Rev. Biochem. 88, 691-724. https://doi.org/10.1146/annurev-biochem-013118-111153
  6. Delgehyr, N., Meunier, A., Faucourt, M., Bosch Grau, M., Strehl, L., Janke, C., and Spassky, N. (2015). Ependymal cell differentiation, from monociliated to multiciliated cells. Methods Cell Biol. 127, 19-35. https://doi.org/10.1016/bs.mcb.2015.01.004
  7. Dirksen, E.R. (1971). Centriole morphogenesis in developing ciliated epithelium of the mouse oviduct. J. Cell Biol. 51, 286-302. https://doi.org/10.1083/jcb.51.1.286
  8. Faber, J. and Nieuwkoop, P.D. (1994). Normal Table of Xenopus laevis (Daudin) (New York: Garland Science).
  9. Fliegauf, M., Benzing, T., and Omran, H. (2007). When cilia go bad: cilia defects and ciliopathies. Nat. Rev. Mol. Cell Biol. 8, 880-893. https://doi.org/10.1038/nrm2278
  10. Gomperts, B.N., Gong-Cooper, X., and Hackett, B.P. (2004). Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells. J. Cell Sci. 117, 1329-1337. https://doi.org/10.1242/jcs.00978
  11. Gonzalez-Mariscal, L., Namorado, M.C., Martin, D., Luna, J., Alarcon, L., Islas, S., Valencia, L., Muriel, P., Ponce, L., and Reyes, J.L. (2000). Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules. Kidney Int. 57, 2386-2402. https://doi.org/10.1046/j.1523-1755.2000.00098.x
  12. Kim, S., Ma, L., Shokhirev, M.N., Quigley, I., and Kintner, C. (2018). Multicilin and activated E2f4 induce multiciliated cell differentiation in primary fibroblasts. Sci. Rep. 8, 12369.
  13. Klos Dehring, D., Vladar, E., Werner, M., Mitchell, J., Hwang, P., and Mitchell, B. (2013). Deuterosome-mediated centriole biogenesis. Dev. Cell 27, 103-112.
  14. Labedan, P., Matthews, C., Kodjabachian, L., Cremer, H., Tissir, F., and Boutin, C. (2016). Dissection and staining of mouse brain ventricular wall for the analysis of ependymal cell cilia organization. Bio Protoc. 6, e1757.
  15. Matsuda, T. and Cepko, C.L. (2007). Controlled expression of transgenes introduced by in vivo electroporation. Proc. Natl. Acad. Sci. U. S. A. 104, 1027-1032. https://doi.org/10.1073/pnas.0610155104
  16. Mercey, O., Al Jord, A., Rostaing, P., Mahuzier, A., Fortoul, A., Boudjema, A., Faucourt, M., Spassky, N., and Meunier, A. (2019a). Dynamics of centriole amplification in centrosome-depleted brain multiciliated progenitors. Sci. Rep. 9, 13060.
  17. Mercey, O., Levine, M.S., LoMastro, G.M., Rostaing, P., Brotslaw, E., Gomez, V., Kumar, A., Spassky, N., Mitchell, B.J., Meunier, A., et al. (2019b). Massive centriole production can occur in the absence of deuterosomes in multiciliated cells. Nat. Cell Biol. 21, 1544-1552. https://doi.org/10.1038/s41556-019-0427-x
  18. Mirvis, M., Stearns, T., and James Nelson, W. (2018). Cilium structure, assembly, and disassembly regulated by the cytoskeleton. Biochem. J. 475, 2329-2353. https://doi.org/10.1042/BCJ20170453
  19. Mirzadeh, Z., Doetsch, F., Sawamoto, K., Wichterle, H., and Alvarez-Buylla, A. (2010). The subventricular zone en-face: wholemount staining and ependymal flow. J. Vis. Exp. (39), 1938.
  20. Mitchell, B., Jacobs, R., Li, J., Chien, S., and Kintner, C. (2007). A positive feedback mechanism governs the polarity and motion of motile cilia. Nature 447, 97-101. https://doi.org/10.1038/nature05771
  21. Nanjundappa, R., Kong, D., Shim, K., Stearns, T., Brody, S.L., Loncarek, J., and Mahjoub, M.R. (2019). Regulation of cilia abundance in multiciliated cells. Elife 8, e44039.
  22. Ohata, S., Nakatani, J., Herranz-Perez, V., Cheng, J., Belinson, H., Inubushi, T., Snider, W., Garcia-Verdugo, J., Wynshaw-Boris, A., and Alvarez-Buylla, A. (2014). Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus. Neuron 83, 558-571. https://doi.org/10.1016/j.neuron.2014.06.022
  23. Park, S., Lee, H., Lee, J., Park, E., and Park, S. (2019). Ependymal cells require Anks1a for their proper development. Mol. Cells 42, 245-251.
  24. Redmond, S.A., Figueres-Onate, M., Obernier, K., Nascimento, M.A., Parraguez, J.I., Lopez-Mascaraque, L., Fuentealba, L.C., and Alvarez-Buylla, A. (2019). Development of ependymal and postnatal neural stem cells and their origin from a common embryonic progenitor. Cell Rep. 27, 429-441. e3. https://doi.org/10.1016/j.celrep.2019.01.088
  25. Revinski, D.R., Zaragosi, L., Boutin, C., Ruiz-Garcia, S., Deprez, M., Thome, V., Rosnet, O., Gay, A., Mercey, O., Paquet, A., et al. (2018). CDC20B is required for deuterosome-mediated centriole production in multiciliated cells. Nat. Commun. 9, 4668.
  26. Ryu, H., Lee, H., Lee, J., Noh, H., Shin, M., Kumar, V., Hong, S., Kim, J., and Park, S. (2021). The molecular dynamics of subdistal appendages in multi-ciliated cells. Nat. Commun. 12, 612.
  27. Shahid, U. and Singh, P. (2018). Emerging picture of deuterosome-dependent centriole amplification in MCCs. Cells 7, 152.
  28. Sir, J.H., Barr, A.R., Nicholas, A.K., Carvalho, O.P., Khurshid, M., Sossick, A., Reichelt, S., D'Santos, C., Woods, C.G., and Gergely, F. (2011). A primary microcephaly protein complex forms a ring around parental centrioles. Nat. Genet. 43, 1147-1153. https://doi.org/10.1038/ng.971
  29. Spassky, N. and Meunier, A. (2017). The development and functions of multiciliated epithelia. Nat. Rev. Mol. Cell Biol. 18, 423-436. https://doi.org/10.1038/nrm.2017.21
  30. Spassky, N., Merkle, F.T., Flames, N., Tramontin, A.D., Garcia-Verdugo, J.M., and Alvarez-Buylla, A. (2005). Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J. Neurosci. 25, 10-18. https://doi.org/10.1523/JNEUROSCI.1108-04.2005
  31. Umair, Z., Kumar, V., Goutam, R.S., Kumar, S., Lee, U., and Kim, J. (2021). Goosecoid controls neuroectoderm specification via dual circuits of direct repression and indirect stimulation in Xenopus embryos. Mol. Cells 44, 723-735. https://doi.org/10.14348/molcells.2021.0055
  32. Vladar, E.K. and Stearns, T. (2007). Molecular characterization of centriole assembly in ciliated epithelial cells. J. Cell Biol. 178, 31-42. https://doi.org/10.1083/jcb.200703064
  33. Weibel, M., Pettmann, B., Artault, J., Sensenbrenner, M., and Labourdette, G. (1986). Primary culture of rat ependymal cells in serum-free defined medium. Brain Res. 25, 199-209. https://doi.org/10.1016/0165-3806(86)90209-9
  34. Winey, M. and O'Toole, E. (2014). Centriole structure. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130457.
  35. Wloga, D., Joachimiak, E., Louka, P., and Gaertig, J. (2017). Posttranslational modifications of tubulin and cilia. Cold Spring Harb. Perspect. Biol. 9, a028159.
  36. Zhao, H., Chen, Q., Fang, C., Huang, Q., Zhou, J., Yan, X., and Zhu, X. (2019). Parental centrioles are dispensable for deuterosome formation and function during basal body amplification. EMBO Rep. 20, e46735.
  37. Zhao, H., Zhu, L., Zhu, Y., Cao, J., Li, S., Huang, Q., Xu, T., Huang, X., Yan, X., and Zhu, X. (2013). The Cep63 paralogue Deup1 enables massive de novo centriole biogenesis for vertebrate multiciliogenesis. Nat. Cell Biol. 15, 1434-1444. https://doi.org/10.1038/ncb2880