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Volume 51 Issue 9
Sep.  2024
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Article Contents

microRNA-2184 orchestrates Mauthner-cell axon regeneration in zebrafish via syt3 modulation

doi: 10.1016/j.jgg.2024.03.016
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This work was supported by the Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220002), the National Natural Science Foundation of China (82071357), and the Ministry of Science and Technology of China (2019YFA0405600 to B.H.).

  • Received Date: 2024-03-26
  • Accepted Date: 2024-03-30
  • Rev Recd Date: 2024-03-30
  • Available Online: 2025-06-06
  • Publish Date: 2024-04-04
  • MicroRNAs (miRNAs) play a significant role in axon regeneration following spinal cord injury. However, the functions of numerous miRNAs in axon regeneration within the central nervous system (CNS) remain largely unexplored. Here, we elucidate the positive role of microRNA-2184 (miR-2184) in axon regeneration within zebrafish Mauthner cells (M-cells). The upregulation of miR-2184 in a single M-cell can facilitate axon regeneration, while the specific sponge-induced silencing of miR-2184 leads to impeded regeneration. We show that syt3, a downstream target of miR-2184, negatively regulates axon regeneration, and the regeneration suppression modulated by syt3 depends on its binding to Ca2+. Furthermore, pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration. Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3, providing valuable insights into potential therapeutic strategies.
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  • Adula, K.P., Shorey, M., Chauhan, V., Nassman, K., Chen, S.F., Rolls, M.M., Sagasti, A., 2022. The MAP3Ks DLK and LZK direct diverse responses to axon damage in zebrafish peripheral neurons. J. Neurosci. 42, 6195-6210.
    Awasthi, A., Ramachandran, B., Ahmed, S., Benito, E., Shinoda, Y., Nitzan, N., Heukamp, A., Rannio, S., Martens, H., Barth, J., et al., 2019. Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting. Science 363, eaav1483.
    Bradbury, E.J., Burnside, E.R., 2019. Moving beyond the glial scar for spinal cord repair. Nat. Commun. 10, 3879.
    Canty, A.J., Huang, L., Jackson, J.S., Little, G.E., Knott, G., Maco, B., De Paola, V., 2013. In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits. Nat. Commun. 4, 2038.
    Carthew, R.W., Sontheimer, E.J., 2009. Origins and mechanisms of miRNAs and siRNAs. Cell 136, 642-655.
    Chen, M., Huang, R.C., Yang, L.Q., Ren, D.L., Hu, B., 2019. In vivo imaging of evoked calcium responses indicates the intrinsic axonal regenerative capacity of zebrafish. FASEB J. 33, 7721-7733.
    Curcio, M., Bradke, F., 2018. Axon regeneration in the central nervous system: facing the challenges from the inside. Annu. Rev. Cell Dev. Biol. 34, 495-521.
    Diekmann, H., Kalbhen, P., Fischer, D., 2015. Active mechanistic target of rapamycin plays an ancillary rather than essential role in zebrafish CNS axon regeneration. Front. Cell. Neurosci. 9, 251.
    Diener, C., Keller, A., Meese, E., 2022. Emerging concepts of miRNA therapeutics: from cells to clinic. Trends Genet. 38, 613-626.
    Dillon, C., Goda, Y., 2005. The actin cytoskeleton: integrating form and function at the synapse. Annu. Rev. Neurosci. 28, 25-55.
    Disner, G.R., Falcao, M.A.P., Lima, C., Lopes-Ferreira, M., 2021. In silico target prediction of overexpressed microRNAs from LPS-challenged zebrafish (Danio rerio) treated with the novel anti-Inflammatory peptide TnP. Int. J. Mol. Sci. 22, 7117.
    Ebert, M.S., Neilson, J.R., Sharp, P.A., 2007. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat. Methods 4, 721-726.
    Egashira, Y., Kumade, A., Ojida, A., Ono, F., 2022. Spontaneously recycling synaptic vesicles constitute readily releasable vesicles in intact neuromuscular synapses. J. Neurosci. 42, 3523-3536.
    Ferragut Cardoso, A.P., Banerjee, M., Nail, A.N., Lykoudi, A., States, J.C., 2021. miRNA dysregulation is an emerging modulator of genomic instability. Semin. Cancer Biol. 76, 120-131.
    Ghibaudi, M., Boido, M., Vercelli, A., 2017. Functional integration of complex miRNA networks in central and peripheral lesion and axonal regeneration. Prog. Neurobiol. 158, 69-93.
    Giraldez, A.J., Cinalli, R.M., Glasner, M.E., Enright, A.J., Thomson, J.M., Baskerville, S., Hammond, S.M., Bartel, D.P., Schier, A.F., 2005. MicroRNAs regulate brain morphogenesis in zebrafish. Science 308, 833-838.
    Goda, Y., Stevens, C.F., 1998. Readily releasable pool size changes associated with long term depression. Proc. Natl. Acad. Sci. U. S. A. 95, 1283-1288.
    Gonzalez-Forero, D., Montero, F., Garcia-Morales, V., Dominguez, G., Gomez-Perez, L., Garcia-Verdugo, J.M., Moreno-Lopez, B., 2012. Endogenous Rho-kinase signaling maintains synaptic strength by stabilizing the size of the readily releasable pool of synaptic vesicles. J. Neurosci. 32, 68-84.
    Hammarlund, M., Nix, P., Hauth, L., Jorgensen, E.M., Bastiani, M., 2009. Axon regeneration requires a conserved MAP kinase pathway. Science 323, 802-806.
    Hilbush, B.S., Morgan, J.I., 1994. A third synaptotagmin gene, Syt3, in the mouse. Proc. Natl. Acad. Sci. U. S. A. 91, 8195-8199.
    Hilton, B.J., Husch, A., Schaffran, B., Lin, T.C., Burnside, E.R., Dupraz, S., Schelski, M., Kim, J., Muller, J.A., Schoch, S., et al., 2022. An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury. Neuron 110, 51-69, e57.
    Hu, B.B., Chen, M., Huang, R.C., Huang, Y.B., Xu, Y., Yin, W., Li, L., Hu, B., 2018. In vivo imaging of Mauthner axon regeneration, remyelination and synapses re-establishment after laser axotomy in zebrafish larvae. Exp. Neurol. 300, 67-73.
    Huang, R., Chen, M., Yang, L., Wagle, M., Guo, S., Hu, B., 2017. MicroRNA-133b negatively regulates zebrafish single Mauthner-cell axon regeneration through targeting tppp3 in Vivo. Front. Mol. Neurosci. 10, 375.
    Hui, E., Bai, J., Wang, P., Sugimori, M., Llinas, R.R., Chapman, E.R., 2005. Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis. Proc. Natl. Acad. Sci. U. S. A. 102, 5210-5214.
    Hung, I.C., Hsiao, Y.C., Sun, H.S., Chen, T.M., Lee, S.J., 2016. MicroRNAs regulate gene plasticity during cold shock in zebrafish larvae. BMC Genomics 17, 922.
    Huntwork-Rodriguez, S., Wang, B., Watkins, T., Ghosh, A.S., Pozniak, C.D., Bustos, D., Newton, K., Kirkpatrick, D.S., Lewcock, J.W., 2013. JNK-mediated phosphorylation of DLK suppresses its ubiquitination to promote neuronal apoptosis. J. Cell Biol. 202, 747-763.
    Kaeser, P.S., Regehr, W.G., 2017. The readily releasable pool of synaptic vesicles. Curr. Opin. Neurobiol. 43, 63-70.
    Kim, V.N., Han, J., Siomi, M.C., 2009. Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell Biol. 10, 126-139.
    Lau, K., Lai, K.P., Bao, J.Y., Zhang, N., Tse, A., Tong, A., Li, J.W., Lok, S., Kong, R.Y., Lui, W.Y., et al., 2014. Identification and expression profiling of microRNAs in the brain, liver and gonads of marine medaka (Oryzias melastigma) and in response to hypoxia. PLoS One 9, e110698.
    Li, Y., He, X., Kawaguchi, R., Zhang, Y., Wang, Q., Monavarfeshani, A., Yang, Z., Chen, B., Shi, Z., Meng, H., et al., 2020. Microglia-organized scar-free spinal cord repair in neonatal mice. Nature 587, 613-618.
    Liu, D., Yu, Y., Schachner, M., 2014. Ptena, but not Ptenb, reduces regeneration after spinal cord injury in adult zebrafish. Exp. Neurol. 261, 196-205.
    Mahar, M., Cavalli, V., 2018. Intrinsic mechanisms of neuronal axon regeneration. Nat. Rev. Neurosci. 19, 323-337.
    Martens, S., Kozlov, M.M., McMahon, H.T., 2007. How synaptotagmin promotes membrane fusion. Science 316, 1205-1208.
    Park, K.K., Liu, K., Hu, Y., Smith, P.D., Wang, C., Cai, B., Xu, B., Connolly, L., Kramvis, I., Sahin, M., et al., 2008. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322, 963-966.
    Quan, Y.Z., Wei, W., Ergin, V., Rameshbabu, A.P., Huang, M., Tian, C., Saladi, S.V., Indzhykulian, A.A., Chen, Z.Y., 2023. Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell-like cells in adult mice. Proc. Natl. Acad. Sci. U. S. A. 120, e2215253120.
    Schmidt, J.T., Morgan, P., Dowell, N., Leu, B., 2002. Myosin light chain phosphorylation and growth cone motility. J. Neurobiol. 52, 175-188.
    Smith, P.D., Sun, F., Park, K.K., Cai, B., Wang, C., Kuwako, K., Martinez-Carrasco, I., Connolly, L., He, Z., 2009. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 64, 617-623.
    Snider, W.D., Zhou, F.-Q., Zhong, J., Markus, A., 2002. Signaling the pathway to regeneration. Neuron 35, 13-16.
    Soares, A.R., Pereira, P.M., Santos, B., Egas, C., Gomes, A.C., Arrais, J., Oliveira, J.L., Moura, G.R., Santos, M.A., 2009. Parallel DNA pyrosequencing unveils new zebrafish microRNAs. BMC Genomics 10, 195.
    Srinivasan, G., Kim, J.H., von Gersdorff, H., 2008. The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of Held synapse. J. Neurophysiol. 99, 1810-1824.
    Strickland, I.T., Richards, L., Holmes, F.E., Wynick, D., Uney, J.B., Wong, L.F., 2011. Axotomy-induced miR-21 promotes axon growth in adult dorsal root ganglion neurons. PLoS One 6, e23423.
    Sugita, S., Shin, O.H., Han, W., Lao, Y., Sudhof, T.C., 2002. Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct Ca(2+) affinities. EMBO J. 21, 270-280.
    Tay, Y., Kats, L., Salmena, L., Weiss, D., Tan, S.M., Ala, U., Karreth, F., Poliseno, L., Provero, P., Di Cunto, F., et al., 2011. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147, 344-357.
    Thomson, D.W., Dinger, M.E., 2016. Endogenous microRNA sponges: evidence and controversy. Nat. Rev. Genet. 17, 272-283.
    Vaden, J.H., Banumurthy, G., Gusarevich, E.S., Overstreet-Wadiche, L., Wadiche, J.I., 2019. The readily-releasable pool dynamically regulates multivesicular release. Elife 8, e47434.
    Vrljic, M., Strop, P., Ernst, J.A., Sutton, R.B., Chu, S., Brunger, A.T., 2010. Molecular mechanism of the synaptotagmin-SNARE interaction in Ca2+-triggered vesicle fusion. Nat. Struct. Mol. Biol. 17, 325-331.
    Wei, C., Wang, B., Peng, D., Zhang, X., Li, Z., Luo, L., He, Y., Liang, H., Du, X., Li, S., et al., 2022. Pan-Cancer analysis shows that ALKBH5 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including gliomas. Front. Immunol. 13, 849592.
    Weingarten, D.J., Shrestha, A., Juda-Nelson, K., Kissiwaa, S.A., Spruston, E., Jackman, S.L., 2022. Fast resupply of synaptic vesicles requires synaptotagmin-3. Nature 611, 320-325.
    Wen, H., Linhoff, M.W., McGinley, M.J., Li, G.L., Corson, G.M., Mandel, G., Brehm, P., 2010. Distinct roles for two synaptotagmin isoforms in synchronous and asynchronous transmitter release at zebrafish neuromuscular junction. Proc. Natl. Acad. Sci. U. S. A. 107, 13906-13911.
    Wu, X., Hu, S., Kang, X., Wang, C., 2020. Synaptotagmins: beyond presynaptic neurotransmitter release. Neuroscientist 26, 9-15.
    Xu, J., Mashimo, T., Sudhof, T.C., 2007. Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron 54, 567-581.
    Yan, D., Wu, Z., Chisholm, A.D., Jin, Y., 2009. The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell 138, 1005-1018.
    Yoshimoto, T., Kittaka, M., Doan, A.A.P., Urata, R., Prideaux, M., Rojas, R.E., Harding, C.V., Henry Boom, W., Bonewald, L.F., Greenfield, E.M., et al., 2022. Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection. Nat. Commun. 13, 6648.
    Zhang, H., Kong, Q., Wang, J., Jiang, Y., Hua, H., 2020. Complex roles of cAMP-PKA-CREB signaling in cancer. Exp. Hematol. Oncol. 9, 32.
    Zhang, C., Chen, H., He, Q., Luo, Y., He, A., Tao, A., Yan, J., 2021. Fibrinogen/AKT/Microfilament axis promotes colitis by enhancing vascular permeability. Cell. Mol. Gastroenterol. Hepatol. 11, 683-696.
    Zhao, C., Rao, J.-S., Duan, H., Hao, P., Shang, J., Fan, Y., Zhao, W., Gao, Y., Yang, Z., Sun, Y.E., et al., 2022. Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar. Signal Transduct. Target. Ther. 7, 184.
    Zhou, B., Yu, P., Lin, M.Y., Sun, T., Chen, Y., Sheng, Z.H., 2016. Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits. J. Cell Biol. 214, 103-119.
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