Hcfc1 and Ogt Mediate Zebrafish CNS Regeneration Through Hippo/Yap Signalling

Abstract

Regeneration of the central nervous system (CNS) is a complex and tightly regulated process, yet the precise molecular players and transcriptional regulators involved remain incompletely understood. Here, we identify Host Cell Factor-1 (Hcfc1), a transcriptional co-regulator, and O-GlcNAc transferase (Ogt), which cleaves and O-GlcNAcylates HCF-1, as crucial regulators of zebrafish brain and retinal regeneration. We uncover their interplay with the Hippo/Yap signalling pathway, a well-known regulator of tissue growth and repair. Knockdown of hcfc1a/b or Ogt activity inhibition disrupts regeneration and reduces Yap levels, while Yap inhibition alone also impairs regeneration. Strikingly, overexpression of constitutively active Yap5SA rescues proliferation defects caused by Hcfc1 depletion and Ogt inhibition in retinal regeneration. Further, yap1 knockdown reduces hcfc1a/b levels, suggesting potential feedback regulation. These findings reveal a previously unrecognised regulatory axis involving Hcfc1, Ogt, and the Hippo/Yap pathway, which governs CNS regeneration. Targeting this pathway could offer a strategy for enhancing CNS regeneration.

Keywords

brain / Hcfc1 / Hippo/Yap signalling / Ogt / regeneration / retina / zebrafish

References

[1] H. Grandel and M. Brand, “Comparative Aspects of Adult Neural Stem Cell Activity in Vertebrates,” Development Genes and Evolution 223, no. 1–2 (2013): 131–147, https://doi.org/10.1007/s00427-012-0425-5.

[2] P. Ferretti, “Is There a Relationship Between Adult Neurogenesis and Neuron Generation Following Injury Across Evolution?,” European Journal of Neuroscience 34, no. 6 (2011): 951–962, https://doi.org/10.1111/J.1460-9568.2011.07833.X.

[3] A. Alunni and L. Bally-Cuif, “A Comparative View of Regenerative Neurogenesis in Vertebrates,” Development 143, no. 5 (2016): 741–753, https://doi.org/10.1242/DEV.122796.

[4] G. K. H. Zupanc, “Adult Neurogenesis in the Central Nervous System of Teleost Fish: From Stem Cells to Function and Evolution,” Journal of Experimental Biology 224, no. 8 (2021): jeb226357, https://doi.org/10.1242/JEB.226357/258585.

[5] A. Bringmann, I. Iandiev, T. Pannicke, et al., “Cellular Signaling and Factors Involved in Müller Cell Gliosis: Neuroprotective and Detrimental Effects,” Progress in Retinal and Eye Research 28, no. 6 (2009): 423–451, https://doi.org/10.1016/J.PRETEYERES.2009.07.001.

[6] F. Moreau, S. Patel, M. L. Lauzon, et al., “Cavitation After Acute Symptomatic Lacunar Stroke Depends on Time, Location, and MRI Sequence,” Stroke 43, no. 7 (2012): 1837–1842, https://doi.org/10.1161/STROKEAHA.111.647859.

[7] S. Gabel, E. Koncina, G. Dorban, et al., “Inflammation Promotes a Conversion of Astrocytes Into Neural Progenitor Cells via NF-κB Activation,” Molecular Neurobiology 53, no. 8 (2016): 5041–5055, https://doi.org/10.1007/S12035-015-9428-3.

[8] J. Altman and G. D. Das, “Autoradiographic and Histological Evidence of Postnatal Hippocampal Neurogenesis in Rats,” Journal of Comparative Neurology 124, no. 3 (1965): 319–335, https://doi.org/10.1002/CNE.901240303.

[9] P. S. Eriksson, E. Perfilieva, T. Björk-Eriksson, et al., “Neurogenesis in the Adult Human Hippocampus,” Nature Medicine 4, no. 11 (1998): 1313–1317, https://doi.org/10.1038/3305.

[10] V. Tropepe, B. L. K. Coles, B. J. Chiasson, et al., “Retinal Stem Cells in the Adult Mammalian Eye,” Science (1979) 287, no. 5460 (2000): 2032–2036, https://doi.org/10.1126/science.287.5460.2032.

[11] B. L. K. Coles, B. Angénieux, T. Inoue, et al., “Facile Isolation and the Characterization of Human Retinal Stem Cells,” Proceedings of the National Academy of Sciences of the United States of America 101, no. 44 (2004): 15772–15777, https://doi.org/10.1073/PNAS.0401596101/SUPPL_FILE/01596FIG7.JPG.

[12] G. C. Martínez-Navarrete, A. Angulo, J. Martín-Nieto, and N. Cuenca, “Gradual Morphogenesis of Retinal Neurons in the Peripheral Retinal Margin of Adult Monkeys and Humans,” Journal of Comparative Neurology 511, no. 4 (2008): 557–580, https://doi.org/10.1002/CNE.21860.

[13] H. Yamashita and M. Sears, “Proof That the Ciliary Epithelium Can Regenerate,” Experimental Eye Research 27, no. 2 (1978): 199–213, https://doi.org/10.1016/0014-4835(78)90089-1.

[14] J. Kaslin, J. Ganz, and M. Brand, “Proliferation, Neurogenesis and Regeneration in the Non-Mammalian Vertebrate Brain,” Philosophical Transactions of the Royal Society, B: Biological Sciences 363, no. 1489 (2007): 101–122, https://doi.org/10.1098/RSTB.2006.2015.

[15] V. Kroehne, D. Freudenreich, S. Hans, J. Kaslin, and M. Brand, “Regeneration of the Adult Zebrafish Brain From Neurogenic Radial Glia-Type Progenitors,” Development 138, no. 22 (2011): 4831–4841, https://doi.org/10.1242/dev.072587.

[16] N. Kyritsis, C. Kizil, S. Zocher, et al., “Acute Inflammation Initiates the Regenerative Response in the Adult Zebrafish Brain,” Science (1979) 338, no. 6112 (2012): 1353–1356, https://doi.org/10.1126/SCIENCE.1228773/SUPPL_FILE/KYRITSIS.SM.PDF.

[17] R. Schmidt, T. Beil, U. Strähle, and S. Rastegar, “Stab Wound Injury of the Zebrafish Adult Telencephalon: A Method to Investigate Vertebrate Brain Neurogenesis and Regeneration,” 90, no. 90 (2014): 51753, https://doi.org/10.3791/51753.

[18] H. Grandel, J. Kaslin, J. Ganz, I. Wenzel, and M. Brand, “Neural Stem Cells and Neurogenesis in the Adult Zebrafish Brain: Origin, Proliferation Dynamics, Migration and Cell Fate,” Developmental Biology 295, no. 1 (2006): 263–277, https://doi.org/10.1016/j.ydbio.2006.03.040.

[19] N. Kishimoto, K. Shimizu, and K. Sawamoto, “Neuronal Regeneration in a Zebrafish Model of Adult Brain Injury,” Disease Models & Mechanisms 5, no. 2 (2012): 200–209, https://doi.org/10.1242/dmm.007336.

[20] A. Zambusi and J. Ninkovic, “Regeneration of the Central Nervous System-Principles From Brain Regeneration in Adult Zebrafish,” World Journal of Stem Cells 12, no. 1 (2020): 8–24, https://doi.org/10.4252/wjsc.v12.i1.8.

[21] D. Goldman, “Müller Glia Cell Reprogramming and Retina Regeneration,” Nature Reviews Neuroscience 15, no. 7 (2014): 431–442, https://doi.org/10.1038/NRN3723.

[22] M. März, R. Schmidt, S. Rastegar, and U. Strahle, “Regenerative Response Following Stab Injury in the Adult Zebrafish Telencephalon,” Developmental Dynamics 240, no. 9 (2011): 2221–2231, https://doi.org/10.1002/DVDY.22710.

[23] B. V. Fausett and D. Goldman, “A Role for α1 Tubulin-Expressing Müller Glia in Regeneration of the Injured Zebrafish Retina,” Journal of Neuroscience 26, no. 23 (2006): 6303–6313, https://doi.org/10.1523/JNEUROSCI.0332-06.2006.

[24] R. Ramachandran, A. Reifler, J. M. Parent, and D. Goldman, “Conditional Gene Expression and Lineage Tracing of Tuba1a Expressing Cells During Zebrafish Development and Retina Regeneration,” Journal of Comparative Neurology 518, no. 20 (2010): 4196–4212, https://doi.org/10.1002/CNE.22448.

[25] P. Hitchcock, M. Ochocinska, A. Sieh, and D. Otteson, “Persistent and Injury-Induced Neurogenesis in the Vertebrate Retina,” Progress in Retinal and Eye Research 23, no. 2 (2004): 183–194, https://doi.org/10.1016/J.PRETEYERES.2004.01.001.

[26] C. Powell, E. Cornblath, F. Elsaeidi, J. Wan, and D. Goldman, “Zebrafish Müller Glia-Derived Progenitors Are Multipotent, Exhibit Proliferative Biases and Regenerate Excess Neurons OPEN,” Nature Publishing Group 6, no. 1 (2016): 24851, https://doi.org/10.1038/srep24851.

[27] K. Howe, M. D. Clark, C. F. Torroja, et al., “The Zebrafish Reference Genome Sequence and Its Relationship to the Human Genome,” Nature 496 (2013): 498–503, https://doi.org/10.1038/nature12111.

[28] B. Adolf, P. Chapouton, C. S. Lam, et al., “Conserved and Acquired Features of Adult Neurogenesis in the Zebrafish Telencephalon,” Developmental Biology 295, no. 1 (2006): 278–293, https://doi.org/10.1016/J.YDBIO.2006.03.023.

[29] B. W. Lindsey, A. Darabie, and V. Tropepe, “The Cellular Composition of Neurogenic Periventricular Zones in the Adult Zebrafish Forebrain,” Journal of Comparative Neurology 520, no. 10 (2012): 2275–2316, https://doi.org/10.1002/CNE.23065.

[30] M. Labusch, L. Mancini, D. Morizet, and L. Bally-Cuif, “Conserved and Divergent Features of Adult Neurogenesis in Zebrafish,” Frontiers in Cell and Development Biology 8 (2020): 1–28, https://doi.org/10.3389/fcell.2020.00525.

[31] N. Jurisch-Yaksi, E. Yaksi, C. Kizil, N. Jurisch-Yaksi, E. Yaksi, and C. Kizil, “Radial Glia in the Zebrafish Brain: Functional, Structural, and Physiological Comparison With the Mammalian Glia,” Glia 68, no. 12 (2020): 2451–2470, https://doi.org/10.1002/glia.23849.

[32] M. Perron and W. A. Harris, “Retinal Stem Cells in Vertebrates,” BioEssays 22, no. 8 (2000): 685–688, https://doi.org/10.1002/1521-1878(200008)22:8<685::AID-BIES1>3.0.CO;2-C.

[33] J. M. Angueyra and K. S. Kindt, “Leveraging Zebrafish to Study Retinal Degenerations,” Frontiers in Cell and Developmental Biology 6 (2018): 110, https://doi.org/10.3389/fcell.2018.00110.

[34] R. L. Luciano and A. C. Wilson, “HCF-1 Functions as a Coactivator for the Zinc Finger Protein Krox20,” Journal of Biological Chemistry 278, no. 51 (2003): 51116–51124, https://doi.org/10.1074/JBC.M303470200.

[35] L. Huang, L. A. Jolly, S. Willis-Owen, et al., “A Noncoding, Regulatory Mutation Implicates HCFC1 in Nonsyndromic Intellectual Disability,” American Journal of Human Genetics 91, no. 4 (2012): 694–702, https://doi.org/10.1016/J.AJHG.2012.08.011.

[36] L. A. Jolly, L. S. Nguyen, D. Domingo, et al., “HCFC1 Loss-Of-Function Mutations Disrupt Neuronal and Neural Progenitor Cells of the Developing Brain,” Human Molecular Genetics 24, no. 12 (2015): 3335–3347, https://doi.org/10.1093/hmg/ddv083.

[37] J. Wysocka and W. Herr, “The Herpes Simplex Virus VP16-Induced Complex: The Makings of a Regulatory Switch,” Trends in Biochemical Sciences 28, no. 6 (2003): 294–304, https://doi.org/10.1016/S0968-0004(03)00088-4.

[38] S. Tyagi and W. Herr, “E2F1 Mediates DNA Damage and Apoptosis Through HCF-1 and the MLL Family of Histone Methyltransferases,” EMBO Journal 28, no. 20 (2009): 3185–3195, https://doi.org/10.1038/EMBOJ.2009.258/SUPPL_FILE/EMBJ2009258-SUP-0002.PDF.

[39] Z. U. Zargar and S. Tyagi, “Role of Host Cell Factor-1 in Cell Cycle Regulation,” Transcription 3, no. 4 (2012): 187–192, https://doi.org/10.4161/TRNS.20711.

[40] M. Dejosez, J. S. Krumenacker, L. J. Zitur, et al., “Ronin Is Essential for Embryogenesis and the Pluripotency of Mouse Embryonic Stem Cells,” Cell 133, no. 7 (2008): 1162–1174, https://doi.org/10.1016/J.CELL.2008.05.047.

[41] F. Capotosti, S. Guernier, F. Lammers, et al., “O-GlcNAc Transferase Catalyzes Site-Specific Proteolysis of HCF-1,” Cell 144, no. 3 (2011): 376–388, https://doi.org/10.1016/J.CELL.2010.12.030.

[42] E. Julien and W. Herr, “Proteolytic Processing Is Necessary to Separate and Ensure Proper Cell Growth and Cytokinesis Functions of HCF-1,” EMBO Journal 22, no. 10 (2003): 2360–2369, https://doi.org/10.1093/emboj/cdg242.

[43] T. Bhuiyan, P. Waridel, V. Kapuria, V. Zoete, and W. Herr, “Distinct OGT-Binding Sites Promote HCF-1 Cleavage,” PLoS One 10 (2015): e0136636, https://doi.org/10.1371/journal.pone.0136636.

[44] S. Daou, N. Mashtalir, I. Hammond-Martel, et al., “Crosstalk Between O-GlcNAcylation and Proteolytic Cleavage Regulates the Host Cell Factor-1 Maturation Pathway,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 7 (2011): 2747–2752, https://doi.org/10.1073/PNAS.1013822108/-/DCSUPPLEMENTAL/PNAS.1013822108_SI.PDF.

[45] V. Kapuria, U. F. Rö Hrig, P. Waridel, et al., “The Conserved Threonine-Rich Region of the HCF-1 PRO Repeat Activates Promiscuous OGT:UDP-GlcNAc Glycosylation and Proteolysis Activities,” Journal of Biological Chemistry 293 (2018): 17754–17768, https://doi.org/10.1074/jbc.RA118.004185.

[46] J. Michaud, V. Praz, N. J. Faresse, et al., “HCFC1 Is a Common Component of Active Human CpG-Island Promoters and Coincides With ZNF143, THAP11, YY1, and GABP Transcription Factor Occupancy,” Genome Research 23, no. 6 (2013): 907–916, https://doi.org/10.1101/GR.150078.112.

[47] H. C. Yu, J. L. Sloan, G. Scharer, et al., “An X-Linked Cobalamin Disorder Caused by Mutations in Transcriptional Coregulator HCFC1,” American Journal of Human Genetics 93, no. 3 (2013): 506–514, https://doi.org/10.1016/j.ajhg.2013.07.022.

[48] M. Dejosez, S. S. Levine, G. M. Frampton, et al., “Ronin/Hcf-1 Binds to a Hyperconserved Enhancer Element and Regulates Genes Involved in the Growth of Embryonic Stem Cells,” Genes & Development 24, no. 14 (2010): 1479–1484, https://doi.org/10.1101/GAD.1935210.

[49] S. Minocha and W. Herr, “Cortical and Commissural Defects Upon HCF-1 Loss in Nkx2.1-Derived Embryonic Neurons and Glia,” Developmental Neurobiology 79, no. 6 (2019): 578–595, https://doi.org/10.1002/dneu.22704.

[50] V. L. Castro, J. F. Reyes, N. G. Reyes-Nava, D. Paz, and A. M. Quintana, “Hcfc1a Regulates Neural Precursor Proliferation and asxl1 Expression in the Developing Brain,” BMC Neuroscience 21, no. 1 (2020): 1–17, https://doi.org/10.1186/S12868-020-00577-1/FIGURES/10.

[51] A. M. Quintana, E. A. Geiger, N. Achilly, et al., “Hcfc1b, a Zebrafish Ortholog of HCFC1, Regulates Craniofacial Development by Modulating Mmachc Expression,” Developmental Biology 396, no. 1 (2014): 94–106, https://doi.org/10.1016/J.YDBIO.2014.09.026.

[52] A. M. Quintana, H. C. Yu, A. Brebner, et al., “Mutations in THAP11 Cause an Inborn Error of Cobalamin Metabolism and Developmental Abnormalities,” Human Molecular Genetics 26, no. 15 (2017): 2838–2849, https://doi.org/10.1093/hmg/ddx157.

[53] P. P. Srivastava, S. Bhasin, S. S. Shankaran, C. Roger, R. Ramachandran, and S. Minocha, “A Reproducible Method to Study Traumatic Injury-Induced Zebrafish Brain Regeneration,” Biology Methods & Protocols 9, no. 1 (2024): bpae073, https://doi.org/10.1093/BIOMETHODS/BPAE073.

[54] V. L. Castro, D. Paz, V. Virrueta, et al., “Missense and Nonsense Mutations of the Zebrafish Hcfc1a Gene Result in Contrasting mTor and Radial Glial Phenotypes,” Gene 864 (2023): 147290, https://doi.org/10.1016/J.GENE.2023.147290.

[55] R. Chakraborty, H. Tabassum, and S. Parvez, “Dantrolene Alleviates Mitochondrial Dysfunction and Neuroinflammation in Traumatic Brain Injury by Modulating the NF-ĸβ/Akt Pathway,” Biochemical Pharmacology 224 (2024): 116244, https://doi.org/10.1016/J.BCP.2024.116244.

[56] S. Minocha, T. L. Sung, D. Villeneuve, F. Lammers, and W. Herr, “Compensatory Embryonic Response to Allele-Specific Inactivation of the Murine X-Linked Gene Hcfc1,” Developmental Biology 412, no. 1 (2016): 1–17, https://doi.org/10.1016/J.YDBIO.2016.02.019.

[57] S. Minocha, S. Bessonnard, T. L. Sung, C. Moret, D. B. Constam, and W. Herr, “Epiblast-Specific Loss of HCF-1 Leads to Failure in Anterior-Posterior Axis Specification,” Developmental Biology 418, no. 1 (2016): 75–88, https://doi.org/10.1016/J.YDBIO.2016.08.008.

[58] R. F. Ortiz-Meoz, J. Jiang, M. B. Lazarus, et al., “A Small Molecule That Inhibits OGT Activity in Cells,” ACS Chemical Biology 10 (2015): 1392–1397, https://doi.org/10.1021/acschembio.5b00004.

[59] S. E. S. Martin, Z. W. Tan, H. M. Itkonen, et al., “Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors,” Journal of the American Chemical Society 140, no. 42 (2018): 13542–13545, https://doi.org/10.1021/JACS.8B07328.

[60] H. M. Itkonen, S. Minner, I. J. Guldvik, et al., “O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells,” Cancer Research 73, no. 16 (2013): 5277–5287, https://doi.org/10.1158/0008-5472.CAN-13-0549.

[61] S. K. Park, X. Zhou, K. E. Pendleton, et al., “A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron Retention and O-GlcNAc Homeostasis,” Cell Reports 20, no. 5 (2017): 1088–1099, https://doi.org/10.1016/J.CELREP.2017.07.017.

[62] Z. Nan, W. Yang, J. Lyu, et al., “Drosophila Hcf Regulates the Hippo Signaling Pathway via Association With the Histone H3K4 Methyltransferase Trr,” Biochemical Journal 476, no. 4 (2019): 759–768, https://doi.org/10.1042/BCJ20180717.

[63] S. E. Riley, Y. Feng, and C. G. Hansen, “Hippo-Yap/Taz Signalling in Zebrafish Regeneration,” npj Regenerative Medicine 7, no. 1 (2022): 1–16, https://doi.org/10.1038/s41536-022-00209-8.

[64] Q. Jiang, D. Liu, Y. Gong, et al., “Yap Is Required for the Development of Brain, Eyes, and Neural Crest in Zebrafish,” Biochemical and Biophysical Research Communications 384, no. 1 (2009): 114–119, https://doi.org/10.1016/J.BBRC.2009.04.070.

[65] J. Hu, S. Sun, Q. Jiang, et al., “Yes-Associated Protein (Yap) is Required for Early Embryonic Development in Zebrafish (Danio Rerio),” International Journal of Biological Sciences 9, no. 3 (2013): 267–278, https://doi.org/10.7150/IJBS.4887.

[66] C. Wang, X. Zhu, W. Feng, et al., “Verteporfin Inhibits YAP Function Through Up-Regulating 14-3-3σ Sequestering YAP in the Cytoplasm,” American Journal of Cancer Research 6, no. 1 (2015): 27.

[67] B. Zhao, X. Wei, W. Li, et al., “Inactivation of YAP Oncoprotein by the Hippo Pathway Is Involved in Cell Contact Inhibition and Tissue Growth Control,” Genes & Development 21, no. 21 (2007): 2747–2761, https://doi.org/10.1101/gad.1602907.

[68] H. B. Ruan, X. Han, M. D. Li, et al., “O-GlcNAc Transferase/Host Cell Factor C1 Complex Regulates Gluconeogenesis by Modulating PGC-1α Stability,” Cell Metabolism 16, no. 2 (2012): 226–237, https://doi.org/10.1016/J.CMET.2012.07.006.

[69] E. A. Lane, D. W. Choi, L. Garcia-Haro, et al., “HCF-1 Regulates De Novo Lipogenesis Through a Nutrient-Sensitive Complex With ChREBP,” Molecular Cell 75, no. 2 (2019): 357–371.e7, https://doi.org/10.1016/J.MOLCEL.2019.05.019.

[70] D. C. Love, M. W. Krause, and J. A. Hanover, “O-GlcNAc Cycling: Emerging Roles in Development and Epigenetics,” Seminars in Cell & Developmental Biology 21, no. 6 (2010): 646–654, https://doi.org/10.1016/J.SEMCDB.2010.05.001.

[71] H. Honkoop, D. E. M. de Bakker, A. Aharonov, et al., “Single-Cell Analysis Uncovers That Metabolic Reprogramming by ErbB2 Signaling Is Essential for Cardiomyocyte Proliferation in the Regenerating Heart,” eLife 8 (2019): e50163, https://doi.org/10.7554/ELIFE.50163.

[72] J. W. Sinclair, D. R. Hoying, E. Bresciani, et al., “The Warburg Effect Is Necessary to Promote Glycosylation in the Blastema During Zebrafish Tail Regeneration,” NPJ Regenerative Medicine 6, no. 1 (2021): 1–16, https://doi.org/10.1038/s41536-021-00163-x.

[73] A. I. Mahmoud, “Metabolic Switches During Development and Regeneration,” Development 150, no. 20 (2023): dev202008, https://doi.org/10.1242/dev.202008.

[74] F. X. Yu, B. Zhao, and K. L. Guan, “Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer,” Cell 163, no. 4 (2015): 811–828, https://doi.org/10.1016/J.CELL.2015.10.044.

[75] P. Guo, S. Wan, and K. Guan, “The Hippo Pathway: Organ Size Control and Beyond,” Pharmacological Reviews 77, no. 2 (2025): 100031, https://doi.org/10.1016/J.PHARMR.2024.100031.

[76] I. M. Moya and G. Halder, “Hippo–YAP/TAZ Signalling in Organ Regeneration and Regenerative Medicine,” Nature Reviews Molecular Cell Biology 20, no. 4 (2018): 211–226, https://doi.org/10.1038/s41580-018-0086-y.

[77] C. Peng, Y. Zhu, W. Zhang, et al., “Regulation of the Hippo-YAP Pathway by Glucose Sensor O-GlcNAcylation,” Molecular Cell 68, no. 3 (2017): 591–604.e5, https://doi.org/10.1016/J.MOLCEL.2017.10.010.

[78] Z. Zhong, Z. Jiao, and F. X. Yu, “The Hippo Signaling Pathway in Development and Regeneration,” Cell Reports 43, no. 3 (2024): 113926, https://doi.org/10.1016/J.CELREP.2024.113926.

[79] V. L. Castro and A. M. Quintana, “The Role of HCFC1 in Syndromic and Non-Syndromic Intellectual Disability,” Medical Research Archives 8, no. 6 (2020): 10-18103, https://doi.org/10.18103/MRA.V8I6.2122.

[80] V. Kapuria, Ayushma, W. Herr, and S. Minocha, “HCF-1 as a Key Modulator of OGT Function and O-GlcNAcylation in the Liver,” Scientific Reports 15, no. 1 (2025): 28328, https://doi.org/10.1038/S41598-025-11813-1.

[81] M. Ali, H. Tabassum, M. M. Alam, and S. Parvez, “N-Acetyl-l-Cysteine Ameliorates Mitochondrial Dysfunction in Ischemia/Reperfusion Injury via Attenuating Drp-1 Mediated Mitochondrial Autophagy,” Life Sciences 293 (2022): 120338, https://doi.org/10.1016/J.LFS.2022.120338.

[82] M. Salman, H. Tabassum, and S. Parvez, “Tannic Acid Provides Neuroprotective Effects Against Traumatic Brain Injury Through the PGC-1α/Nrf2/HO-1 Pathway,” Molecular Neurobiology 57, no. 6 (2020): 2870–2885, https://doi.org/10.1007/S12035-020-01924-3/FIGURES/10.

[83] M. C. Senut, A. Gulati-Leekha, and D. Goldman, “An Element in the α1-Tubulin Promoter Is Necessary for Retinal Expression During Optic Nerve Regeneration but Not After Eye Injury in the Adult Zebrafish,” Journal of Neuroscience 24, no. 35 (2004): 7663–7673, https://doi.org/10.1523/JNEUROSCI.2281-04.2004.

[84] P. Sharma and R. Ramachandran, “Retina Injury and Retina Tissue Preparation to Study Regeneration in Zebrafish,” Bio-Protocol 9, no. 24 (2019): e3466, https://doi.org/10.21769/BIOPROTOC.3466.

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2025 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.