义乌小鲵肢体再生及其分子机制
收稿日期: 2024-11-11
修回日期: 2025-01-17
网络出版日期: 2025-05-07
基金资助
国家自然科学基金项目(32370454);浙江省重点研发项目(2021C02044);金华市生态环境局义乌分局珍稀濒危野生动物(义乌小鲵)抢救保护行动项目(ZXZJZC2022331GK);永康市野生动物资源本底调查项目资助
The molecular mechanism of limb regeneration of Hynobius yiwuensis
Received date: 2024-11-11
Revised date: 2025-01-17
Online published: 2025-05-07
Supported by
National Natural Science Foundation of China(32370454);Key R&D Program of Zhejiang Province(2021C02044);Rescue and Conservation Project for Rare and Endangered Wildlife (Hynobius yiwuensis) Funded by the Yiwu Branch of the Jinhua Ecological Environment Bureau(ZXZJZC2022331GK);Wildlife Resource Background Survey Project of Yongkang City
陈昊, 董瑞, 王岩峰, 谢净倍, 张招旭, 郑荣泉 . 义乌小鲵肢体再生及其分子机制[J]. 遗传, 2025 , 47(9) : 1032 -1041 . DOI: 10.16288/j.yczz.24-326
Hynobius yiwuensis is a vulnerable species endemic to China, restricted to specific hilly regions in Zhejiang Province. This study employed stereomicroscopy to examine the limb regeneration process in H. yiwuensis and utilized transcriptome sequencing to analyze differentially expressed genes. The results indicate that H. yiwuensis possesses strong regenerative capabilities, with the regeneration process comprising four stages: wound healing, tissue dissolution and dedifferentiation, blastema formation, and morphogenesis followed by redifferentiation. Transcriptome analysis identified numerous differentially expressed genes during limb regeneration, exhibiting distinct expression patterns at various time points post-amputation. Key differentially expressed genes were identified, including IL10, associated with cellular immunity and inflammation; TGFβ3, involved in early muscle tissue regeneration; and MMPs, implicated in tissue remodeling. qRT-PCR validation of selected differentially expressed genes confirmed the reliability of the transcriptome sequencing data. Preliminary findings suggest that H. yiwuensis regulates limb regeneration and promotes scar-free tissue repair through signaling pathways such as Wnt/β-catenin, TGFβ, and BMP.
| [1] | Fei XM. Hynobius yiwuensis population resources investigation, embryonic development and genetic diversity research[Dissertation]. Zhejiang Normal University, 2020. |
| 费潇鸣. 义乌小鲵种群资源调查、胚胎发育及遗传多样性研究[学位论文]. 浙江师范大学, 2020. | |
| [2] | Fei L, Ye CY, Hu SQ, eds. Fauna Sinica: Amphibia, Volume 1, Caudata. Beijing: Science Press, 2006. |
| 费梁, 叶昌媛, 胡淑琴编著. 中国动物志两栖纲(上卷)有尾目. 北京: 科学出版社, 2006. | |
| [3] | Xie JB, Fei XM, Lou XB, Zhang JC, Huang JC. Effects of rearing density and food density on intraspecific competition rate in Hynobius yiwuensis. Jiangxi Fish Sci Technol, 2022, (2): 7-9. |
| 谢净倍, 费潇鸣, 楼晓波, 张建春, 黄建成. 养殖密度和饵料密度对义乌小鲵同种相残率的影响. 江西水产科技, 2022, (2): 7-9. | |
| [4] | Ivankovic M, Haneckova R, Thommen A, Grohme MA, Vila-Farré M, Werner S, Rink JC. Model systems for regeneration: planarians. Development, 2019, 146(17): dev167684. |
| [5] | Maden M, Varholick JA. Model systems for regeneration: the spiny mouse, Acomys cahirinus. Development, 2020, 147(4): dev167718. |
| [6] | Marques IJ, Lupi E, Mercader N. Model systems for regeneration: zebrafish. Development, 2019, 146(18): dev167692. |
| [7] | Tang J. Multi-Omics analysis of limb regeneration in Cynops orientalis[Dissertation]. Northwest University, 2020. |
| 唐婕. 东方蝾螈肢体再生的多组学分析[学位论文]. 西北大学, 2020. | |
| [8] | Mahapatra C, Naik P, Swain SK, Mohapatra PP. Unravelling the limb regeneration mechanisms of Polypedates maculatus, a sub-tropical frog, by transcriptomics. BMC Genomics, 2023, 24(1): 122. |
| [9] | Tan H, Wen XM, Wang X, Ye G, Chen FL. Progress of mechanisms regulating dedifferentiation of terminally differentiated cells during salamander limb regeneration. Chin Bull Life Sci, 2021, 33(2): 199-204. |
| 谭泓, 温晓敏, 王雪, 叶岗, 陈富林. 蝾螈肢体再生中终末分化细胞去分化调控机制的研究进展. 生命科学, 2021, 33(2): 199-204. | |
| [10] | Denis JF, Sader F, Gatien S, Villiard É, Philip A, Roy S. Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration. Development, 2016, 143(19): 3481-3490. |
| [11] | Kurabuchi S, Inoue S. Denervation effects on limb regeneration in postmetamorphic Xenopus laevis: (regeneration/ denervation/Xenopus/limb). Dev Growth Differ, 1983, 25(5): 463-467. |
| [12] | Hoppler S, Conlon FL. Xenopus: experimental access to cardiovascular development, regeneration discovery, and cardiovascular heart-defect modeling. Cold Spring Harb Perspect Biol, 2020, 12(6): a037200. |
| [13] | Everson KM, Gray LN, Jones AG, Lawrence NM, Foley ME, Sovacool KL, Kratovil JD, Hotaling S, Hime PM, Storfer A, Parra-Olea G, Percino-Daniel R, Aguilar- Miguel X, O'Neill EM, Zambrano L, Shaffer HB, Weisrock DW. Geography is more important than life history in the recent diversification of the tiger salamander complex. Proc Natl Acad Sci USA, 2021, 118(17): e2014719118. |
| [14] | Abe G, Hayashi T, Yoshida K, Yoshida T, Kudoh H, Sakamoto J, Konishi A, Kamei Y, Takeuchi T, Tamura K, Yokoyama H. Insights regarding skin regeneration in non-amniote vertebrates: skin regeneration without scar formation and potential step-up to a higher level of regeneration. Semin Cell Dev Biol, 2020, 100: 109-121. |
| [15] | Satoh A, Gardiner DM, Bryant SV, Endo T. Nerve-induced ectopic limb blastemas in the Axolotl are equivalent to amputation-induced blastemas. Dev Biol, 2007, 312(1): 231-244. |
| [16] | Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, Amit I, Adiconis X, Fan L, Raychowdhury R, Zeng QD, Chen ZH, Mauceli E, Hacohen N, Gnirke A, Rhind N, Di Palma F, Birren BW, Nusbaum C, Lindblad-Toh K, Friedman N, Regev A. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol, 2011, 29(7): 644-652. |
| [17] | Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. Nat Genet, 2000, 25(1): 25-29. |
| [18] | Towfic F, VanderPlas S, Oliver CA, Couture O, Tuggle CK, Greenlee MHW, Honavar V. Detection of gene orthology from gene co-expression and protein interaction networks. BMC Bioinformatics, 2010, 11(Suppl 3): S7. |
| [19] | Koonin EV, Fedorova ND, Jackson JD, Jacobs AR, Krylov DM, Makarova KS, Mazumder R, Mekhedov SL, Nikolskaya AN, Rao BS, Rogozin IB, Smirnov S, Sorokin AV, Sverdlov AV, Vasudevan S, Wolf YI, Yin JJ, Natale DA. A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes. Genome Biol, 2004, 5(2): R7. |
| [20] | Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M. The KEGG resource for deciphering the genome. Nucleic Acids Res, 2004, 32(suppl_1): D277-D280. |
| [21] | An S, Schorfheide F. Bayesian analysis of DSGE models. Economet Rev, 2007, 26(2-4): 113-172. |
| [22] | Com E, Boitier E, Marchandeau JP, Brandenburg A, Schroeder S, Hoffmann D, Mally A, Gautier JC. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats. Toxicol Appl Pharmacol, 2012, 258(1): 124-133. |
| [23] | Simon A, Tanaka EM. Limb regeneration. Wiley Interdiscip Rev Dev Biol, 2013, 2(2): 291-300. |
| [24] | Brockes JP. Amphibian limb regeneration: rebuilding a complex structure. Science, 1997, 276(5309): 81-87. |
| [25] | Leigh ND, Dunlap GS, Johnson K, Mariano R, Oshiro R, Wong AY, Bryant DM, Miller BM, Ratner A, Chen A, Ye WW, Haas BJ, Whited JL. Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution. Nat Commun, 2018, 9(1): 5153. |
| [26] | Diogo R, Murawala P, Tanaka EM. Is salamander hindlimb regeneration similar to that of the forelimb? anatomical and morphogenetic analysis of hindlimb muscle regeneration in GFP-transgenic axolotls as a basis for regenerative and developmental studies. J Anat, 2014, 224(4):459-468. |
| [27] | Alibardi L. Review: biological and molecular differences between tail regeneration and limb scarring in lizard: an inspiring model addressing limb regeneration in amniotes. J Exp Zool B Mol Dev Evol, 2017, 328(6): 493-514. |
| [28] | Phipps LS, Marshall L, Dorey K, Amaya E. Model systems for regeneration: Xenopus. Development, 2020, 147(6): dev180844. |
| [29] | Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta, 2011, 1813(5): 878-888. |
| [30] | Dong L, Li M, Tang XH, Huang L, Zhang CC, Guo YH. Research progress on the role of interleukin-10 in maintaining intestinal homeostasis. Chin J Cell Biol, 2023, 45(9): 1409-1418. |
| 童乐, 李梅, 唐小涵, 黄玲, 张长城, 郭煜晖. 白细胞介素-10在维持肠道稳态中的作用研究进展. 中国细胞生物学学报, 2023, 45(9): 1409-1418. | |
| [31] | Shi BM, Xie XD, Wang J. The role of Axin2+cells in periodontal tissue development and regeneration. J Prev Treat Stom Dis, 2022, 30(6): 433-437. |
| 时彬冕, 谢旭东, 王骏. Axin2阳性细胞在牙周组织发育与再生中的作用. 口腔疾病防治, 2022, 30(6): 433-437. | |
| [32] | Liu Q, Cheng Z, Luo LZ, Yang Y, Zhang ZZ, Ma HH, Chen T, Huang X, Lin SY, Jin MJ, Li QX, Li XT. C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis. Oncotarget, 2016, 7(24): 36800-36813. |
| [33] | Wang GR, Xiao C, Wang YT. The role of TGF-β/ Myostatin in skeletal muscle regeneration and fibrosis. Chin J Basic Med Tradit Chin Med, 2012, 18(5): 579-582. |
| 王荣国, 肖诚, 王云亭. TGF-β/Myostatin在骨骼肌再生与纤维化中的作用. 中国中医基础医学杂志, 2012, 18(5): 579-582. | |
| [34] | Lee MS, Wan J, Goldman D. Tgfb3 collaborates with PP2A and notch signaling pathways to inhibit retina regeneration. eLife, 2020, 9: e55137. |
| [35] | Kaminska B, Wesolowska A, Danilkiewicz M. TGF beta signalling and its role in tumour pathogenesis. Acta Biochim Pol, 2005, 52(2): 329-337. |
| [36] | Vinarsky V, Atkinson DL, Stevenson TJ, Keating MT, Odelberg SJ. Normal newt limb regeneration requires matrix metalloproteinase function. Dev Biol, 2005, 279(1): 86-98. |
| [37] | Fan YF, Ye JQ, Shen FX, Zhu YQ, Yeghiazarians Y, Zhu W, Chen YM, Lawton MT, Young WL, Yang GY. Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro. J Cereb Blood Flow Metab, 2008, 28(1): 90-98. |
| [38] | Lin WZ, Zhu XH, Gao L, Mao MY, Gao DM, Huang ZW. Osteomodulin positively regulates osteogenesis through interaction with BMP2. Cell Death Dis, 2021, 12(2): 147. |
| [39] | Chen QQ, Liu QY, Zhang YS, Li SY, Yi S. Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration. Cell Death Dis, 2021, 12(5): 417. |
/
| 〈 |
|
〉 |