De novo centriole formation and the assembly of differentiation inducing molecular complexes in embryonic cells
DOI:
https://doi.org/10.65649/evy0j073Keywords:
Centriole, De novo biogenesis, Embryogenesis, Cell fate determination, Asymmetric Division, Biomolecular condensates, Developmental disordersAbstract
Early embryonic development requires the transformation of a single cell into a complex, patterned organism. This process critically depends on the de novo formation of centrioles, which, unlike the canonical templated duplication in somatic cells, occurs without pre-existing organelles in oocytes and zygotes. This review synthesizes evidence from a systematic analysis of studies across model organisms to propose that de novo centriole biogenesis serves a dual, integrative function. It not only ensures the assembly of the mitotic apparatus but also acts as a fundamental organizing principle for the spatial assembly and asymmetric segregation of macromolecular complexes that induce cell differentiation. We delineate a stage-dependent model, from oogenic predetermination through the first cleavages, demonstrating how the nascent centriole acts as a scaffold for liquid-liquid phase separation (LLPS), co-condensing fate determinants like transcription factors, repressors, and localized mRNAs. Comparative and functional analyses from C. elegans to mice establish a causal link: disrupting centriole assembly or its association with determinants leads to defective asymmetric division and cell fate transformation. We conclude that de novo centriologenesis is the architectonic event that couples cell division with lineage specification, a deeply conserved mechanism whose disruption underpins severe human developmental disorders. The presented integrative model reframes the centrosome as an active conductor of embryonic patterning.
References
Bontems, F., Stein, A., Marlow, F., Lyautey, J., Gupta, T., Mullins, M. C., & Dosch, R. (2009). Bucky ball organizes germ plasm assembly in zebrafish. Current Biology, 19(5), 414–422. https://doi.org/10.1016/j.cub.2009.01.038 DOI: https://doi.org/10.1016/j.cub.2009.01.038
Borrego-Pinto, J., Somogyi, K., Karreman, M. A., König, J., Müller-Reichert, T., Bettencourt-Dias, M., ... & Gönczy, P. (2016). Distinct mechanisms eliminate mother and daughter centrioles in meiosis of starfish oocytes. Journal of Cell Biology, 212(7), 815–827. https://doi.org/10.1083/jcb.201510083 DOI: https://doi.org/10.1083/jcb.201510083
Coelho, P. A., Bury, L., Sharif, B., Riparbelli, M. G., Fu, J., Callaini, G., ... & Glover, D. M. (2013). Spindle formation in the mouse embryo requires Plk4 in the absence of centrioles. Developmental Cell, 27(5), 586–597. https://doi.org/10.1016/j.devcel.2013.09.029 DOI: https://doi.org/10.1016/j.devcel.2013.09.029
Courtois, A., Schuh, M., Ellenberg, J., & Hiiragi, T. (2012). The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development. Journal of Cell Biology, 198(3), 357–370. https://doi.org/10.1083/jcb.201202135 DOI: https://doi.org/10.1083/jcb.201202135
Cowan, C. R., & Hyman, A. A. (2004). Centrosomes direct cell polarity independently of microtubule assembly in C. elegans embryos. Nature, 431(7007), 92–96. https://doi.org/10.1038/nature02825 DOI: https://doi.org/10.1038/nature02825
Dzhindzhev, N. S., Tzolovsky, G., Lipinszki, Z., Schneider, S., Lattao, R., Fu, J., ... & Glover, D. M. (2017). Plk4 phosphorylates Ana2 to trigger Sas6 recruitment and procentriole formation. Current Biology, 27(24), 3527-3538.e4. https://doi.org/10.1016/j.cub.2014.08.061 DOI: https://doi.org/10.1016/j.cub.2014.08.061
Gallo, C. M., Wang, J. T., Motegi, F., & Seydoux, G. (2010). Cytoplasmic partitioning of P granule components is not required to specify the germline in C. elegans. Science, 330(6011), 1685–1689. https://doi.org/10.1126/science.1193697 DOI: https://doi.org/10.1126/science.1193697
Hamill, D. R., Severson, A. F., Carter, J. C., & Bowerman, B. (2002). Centrosome maturation and mitotic spindle assembly in C. elegans require SPD-5, a protein with multiple coiled-coil domains. Developmental Cell, 3(5), 673–684. https://doi.org/10.1016/s1534-5807(02)00327-1 DOI: https://doi.org/10.1016/S1534-5807(02)00327-1
Heasman, J., Wessely, O., Langland, R., Craig, E. J., & Kessler, D. S. (2001). Vegetal localization of maternal mRNAs is disrupted by VegT depletion. Developmental biology, 240(2), 377–386. https://doi.org/10.1006/dbio.2001.0495 DOI: https://doi.org/10.1006/dbio.2001.0495
Hirate, Y., Hirahara, S., Inoue, K., Suzuki, A., Alarcon, V. B., Akimoto, K., Hirai, T., Hara, T., Adachi, M., Chida, K., Ohno, S., Marikawa, Y., Nakao, K., Shimono, A., & Sasaki, H. (2013). Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. Current biology : CB, 23(13), 1181–1194. https://doi.org/10.1016/j.cub.2013.05.014 DOI: https://doi.org/10.1016/j.cub.2013.05.014
Hird, S. N., & White, J. G. (1993). Cortical and cytoplasmic flow polarity in early embryonic cells of Caenorhabditis elegans. Journal of Cell Biology, 121(6), 1343–1355. https://doi.org/10.1083/jcb.121.6.1343 DOI: https://doi.org/10.1083/jcb.121.6.1343
Huang, P., & He, X. (2008). Wnt/β-catenin signaling: new (and old) players and new insights. Current Opinion in Cell Biology, 20(2), 119-125. https://doi.org/10.1016/j.ceb.2008.01.009 DOI: https://doi.org/10.1016/j.ceb.2008.01.009
Jaba, T. (2022). Dasatinib and quercetin: short-term simultaneous administration yields senolytic effect in humans. Issues and Developments in Medicine and Medical Research Vol. 2, 22-31. DOI: https://doi.org/10.9734/bpi/idmmr/v2/15155D
Johnson, M. H., & McConnell, J. M. (2004). Lineage allocation and cell polarity during mouse embryogenesis. Seminars in Cell & Developmental Biology, 15(5), 583–597. https://doi.org/10.1016/j.semcdb.2004.04.002 DOI: https://doi.org/10.1016/j.semcdb.2004.04.002
Klingseisen, A., & Jackson, A. P. (2011). Mechanisms and pathways of growth failure in primordial dwarfism. Genes & Development, 25(19), 2011–2024. https://doi.org/10.1101/gad.169037 DOI: https://doi.org/10.1101/gad.169037
Kloc, M., Zearfoss, N. R., & Etkin, L. D. (2002). Mechanisms of subcellular mRNA localization. Cell, 108(4), 533-544. https://doi.org/10.1016/s0092-8674(02)00651-7 DOI: https://doi.org/10.1016/S0092-8674(02)00651-7
Kono, K., Tamashiro, D. A., & Alarcon, V. B. (2014). Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst. Developmental Biology, 394(1), 142–155. https://doi.org/10.1016/j.ydbio.2014.06.023 DOI: https://doi.org/10.1016/j.ydbio.2014.06.023
Krauss, S. W., Lee, G., Chasis, J. A., Mohandas, N., & Heald, R. (2004). Two protein 4.1 domains essential for mitotic spindle and aster microtubule dynamics and organization in vitro. The Journal of biological chemistry, 279(26), 27591–27598. https://doi.org/10.1074/jbc.M402813200 DOI: https://doi.org/10.1074/jbc.M402813200
Liu, X., Tan, J. P., Schröder, J., Aberkane, A., Ouyang, J. F., Mohenska, M., ... & Polo, J. M. (2021). Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature, 591(7851), 627–632. https://doi.org/10.1038/s41586-021-03372-y DOI: https://doi.org/10.1038/s41586-021-03372-y
Martin, C. A., Ahmad, I., Klingseisen, A., Hussain, M. S., Bicknell, L. S., Leitch, A., ... & Jackson, A. P. (2014). Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nature Genetics, 46(12), 1283–1292. https://doi.org/10.1038/ng.3122 DOI: https://doi.org/10.1038/ng.3122
Pelletier, L., O'Toole, E., Schwager, A., Hyman, A. A., & Müller-Reichert, T. (2006). Centriole assembly in Caenorhabditis elegans. Nature, 444(7119), 619–623. https://doi.org/10.1038/nature05318 DOI: https://doi.org/10.1038/nature05318
Plachta, N., Bollenbach, T., Pease, S., Fraser, S. E., & Pantazis, P. (2011). Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nature Cell Biology, 13(2), 117-123. https://doi.org/10.1038/ncb2154 DOI: https://doi.org/10.1038/ncb2154
Raff, J. W., & Glover, D. M. (1989). Centrosomes, and not nuclei, initiate pole cell formation in Drosophila embryos. Cell, 57(4), 611–619. https://doi.org/10.1016/0092-8674(89)90130-x DOI: https://doi.org/10.1016/0092-8674(89)90130-X
Rodrigues-Martins, A., Riparbelli, M., Callaini, G., Glover, D. M., & Bettencourt-Dias, M. (2007). Revisiting the role of the mother centriole in centriole biogenesis. Science, 316(5827), 1046–1050. https://doi.org/10.1126/science.1142950 DOI: https://doi.org/10.1126/science.1142950
Sardon, T., Peset, I., Petrova, B., & Vernos, I. (2008). Dissecting the role of Aurora A during spindle assembly. The EMBO journal, 27(19), 2567–2579. https://doi.org/10.1038/emboj.2008.173 DOI: https://doi.org/10.1038/emboj.2008.173
Sasaki, H. (2017). Roles and regulations of Hippo signaling during preimplantation mouse development. Development, Growth & Differentiation, 59(1), 12–20. https://doi.org/10.1111/dgd.12335 DOI: https://doi.org/10.1111/dgd.12335
Schubert, C. M., Lin, R., de Vries, C. J., Plasterk, R. H., & Priess, J. R. (2000). MEX-5 and MEX-6 function to establish soma/germline asymmetry in early C. elegans embryos. Molecular Cell, 5(4), 671–682. https://doi.org/10.1016/s1097-2765(00)80246-4 DOI: https://doi.org/10.1016/S1097-2765(00)80246-4
Szollosi, D., Calarco, P., & Donahue, R. P. (1972). Absence of centrioles in the first and second meiotic spindles of mouse oocytes. Journal of Cell Science, 11(2), 521–541. https://doi.org/10.1242/jcs.11.2.521 DOI: https://doi.org/10.1242/jcs.11.2.521
Tang, C. J., Fu, R. H., Wu, K. S., Hsu, W. B., & Tang, T. K. (2009). CPAP is a cell-cycle regulated protein that controls centriole length. Nature cell biology, 11(7), 825–831. https://doi.org/10.1038/ncb1889 DOI: https://doi.org/10.1038/ncb1889
Theusch, E. V., Brown, K. J., & Pelegri, F. (2006). Separate pathways of RNA localization lead to the compartmentalization of the zebrafish germ plasm. Developmental Biology, 292(1), 129–141. https://doi.org/10.1016/j.ydbio.2005.12.045 DOI: https://doi.org/10.1016/j.ydbio.2005.12.045
Tkemaladze, J. (2023). Reduction, proliferation, and differentiation defects of stem cells over time: a consequence of selective accumulation of old centrioles in the stem cells?. Molecular Biology Reports, 50(3), 2751-2761. DOI : https://pubmed.ncbi.nlm.nih.gov/36583780/ DOI: https://doi.org/10.1007/s11033-022-08203-5
Tkemaladze, J. (2024). Editorial: Molecular mechanism of ageing and therapeutic advances through targeting glycative and oxidative stress. Front Pharmacol. 2024 Mar 6;14:1324446. DOI : 10.3389/fphar.2023.1324446. PMID: 38510429; PMCID: PMC10953819. DOI: https://doi.org/10.3389/fphar.2023.1324446
Tkemaladze, J. (2026). Old Centrioles Make Old Bodies. Annals of Rejuvenation Science, 1(1). DOI : https://doi.org/10.65649/yx9sn772 DOI: https://doi.org/10.65649/yx9sn772
Tkemaladze, J. (2026). Visions of the Future. Longevity Horizon, 2(1). DOI : https://doi.org/10.65649/8be27s21 DOI: https://doi.org/10.65649/8be27s21
Weaver, C., & Kimelman, D. (2004). Move it or lose it: axis specification in Xenopus. Development, 131(15), 3491–3499. https://doi.org/10.1242/dev.01284 DOI: https://doi.org/10.1242/dev.01284
Weil, T. T., Parton, R. M., & Davis, I. (2010). Making the message clear: visualizing mRNA localization. Trends in cell biology, 20(7), 380–390. https://doi.org/10.1016/j.tcb.2010.03.006 DOI: https://doi.org/10.1016/j.tcb.2010.03.006
Wong, C., & Stearns, T. (2003). Centrosome number is controlled by a centrosome-intrinsic block to reduplication. Nature Cell Biology, 5(6), 539–544. https://doi.org/10.1038/ncb993 DOI: https://doi.org/10.1038/ncb993
Woodruff, J. B., Ferreira Gomes, B., Widlund, P. O., Mahamid, J., Honigmann, A., & Hyman, A. A. (2017). The Centrosome Is a Selective Condensate that Nucleates Microtubules by Concentrating Tubulin. Cell, 169(6), 1066-1077.e10. https://doi.org/10.1016/j.cell.2017.05.028 DOI: https://doi.org/10.1016/j.cell.2017.05.028
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