IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40486-5.html
   My bibliography  Save this article

Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer

Author

Listed:
  • Valentina Cigliola

    (Duke University
    Duke University Medical Center
    Université Côte d’Azur, Inserm, CNRS, Institut de Biologie Valrose)

  • Adam Shoffner

    (Duke University
    Duke University Medical Center
    Duke University Medical Center)

  • Nutishia Lee

    (Duke University
    Duke University Medical Center)

  • Jianhong Ou

    (Duke University
    Duke University Medical Center)

  • Trevor J. Gonzalez

    (Duke University School of Medicine)

  • Jiaul Hoque

    (Duke University School of Medicine)

  • Clayton J. Becker

    (Duke University
    Duke University Medical Center)

  • Yanchao Han

    (Soochow University)

  • Grace Shen

    (Duke University
    Duke University Medical Center)

  • Timothy D. Faw

    (Duke University
    Duke University School of Medicine
    Duke University)

  • Muhammad M. Abd-El-Barr

    (Duke University Medical Center)

  • Shyni Varghese

    (Duke University School of Medicine
    Duke University
    Duke University)

  • Aravind Asokan

    (Duke University
    Duke University Medical Center
    Duke University School of Medicine
    Duke University)

  • Kenneth D. Poss

    (Duke University
    Duke University Medical Center)

Abstract

Unlike adult mammals, zebrafish regenerate spinal cord tissue and recover locomotor ability after a paralyzing injury. Here, we find that ependymal cells in zebrafish spinal cords produce the neurogenic factor Hb-egfa upon transection injury. Animals with hb-egfa mutations display defective swim capacity, axon crossing, and tissue bridging after spinal cord transection, associated with disrupted indicators of neuron production. Local recombinant human HB-EGF delivery alters ependymal cell cycling and tissue bridging, enhancing functional regeneration. Epigenetic profiling reveals a tissue regeneration enhancer element (TREE) linked to hb-egfa that directs gene expression in spinal cord injuries. Systemically delivered recombinant AAVs containing this zebrafish TREE target gene expression to crush injuries of neonatal, but not adult, murine spinal cords. Moreover, enhancer-based HB-EGF delivery by AAV administration improves axon densities after crush injury in neonatal cords. Our results identify Hb-egf as a neurogenic factor necessary for innate spinal cord regeneration and suggest strategies to improve spinal cord repair in mammals.

Suggested Citation

  • Valentina Cigliola & Adam Shoffner & Nutishia Lee & Jianhong Ou & Trevor J. Gonzalez & Jiaul Hoque & Clayton J. Becker & Yanchao Han & Grace Shen & Timothy D. Faw & Muhammad M. Abd-El-Barr & Shyni Var, 2023. "Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40486-5
    DOI: 10.1038/s41467-023-40486-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40486-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40486-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Fang Sun & Kevin K. Park & Stephane Belin & Dongqing Wang & Tao Lu & Gang Chen & Kang Zhang & Cecil Yeung & Guoping Feng & Bruce A. Yankner & Zhigang He, 2011. "Sustained axon regeneration induced by co-deletion of PTEN and SOCS3," Nature, Nature, vol. 480(7377), pages 372-375, December.
    2. Mark A. Anderson & Joshua E. Burda & Yilong Ren & Yan Ao & Timothy M. O’Shea & Riki Kawaguchi & Giovanni Coppola & Baljit S. Khakh & Timothy J. Deming & Michael V. Sofroniew, 2016. "Astrocyte scar formation aids central nervous system axon regeneration," Nature, Nature, vol. 532(7598), pages 195-200, April.
    3. Trevor J. Gonzalez & Katherine E. Simon & Leo O. Blondel & Marco M. Fanous & Angela L. Roger & Maribel Santiago Maysonet & Garth W. Devlin & Timothy J. Smith & Daniel K. Oh & L. Patrick Havlik & Ruth , 2022. "Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Victoria M. Bedell & Ying Wang & Jarryd M. Campbell & Tanya L. Poshusta & Colby G. Starker & Randall G. Krug II & Wenfang Tan & Sumedha G. Penheiter & Alvin C. Ma & Anskar Y. H. Leung & Scott C. Fahre, 2012. "In vivo genome editing using a high-efficiency TALEN system," Nature, Nature, vol. 491(7422), pages 114-118, November.
    5. Andrea Rossi & Zacharias Kontarakis & Claudia Gerri & Hendrik Nolte & Soraya Hölper & Marcus Krüger & Didier Y. R. Stainier, 2015. "Genetic compensation induced by deleterious mutations but not gene knockdowns," Nature, Nature, vol. 524(7564), pages 230-233, August.
    6. Junsu Kang & Jianxin Hu & Ravi Karra & Amy L. Dickson & Valerie A. Tornini & Gregory Nachtrab & Matthew Gemberling & Joseph A. Goldman & Brian L. Black & Kenneth D. Poss, 2016. "Modulation of tissue repair by regeneration enhancer elements," Nature, Nature, vol. 532(7598), pages 201-206, April.
    7. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    8. Daniel Wehner & Themistoklis M. Tsarouchas & Andria Michael & Christa Haase & Gilbert Weidinger & Michell M. Reimer & Thomas Becker & Catherina G. Becker, 2017. "Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    9. Yi Li & Xuelian He & Riki Kawaguchi & Yu Zhang & Qing Wang & Aboozar Monavarfeshani & Zhiyun Yang & Bo Chen & Zhongju Shi & Huyan Meng & Songlin Zhou & Junjie Zhu & Anne Jacobi & Vivek Swarup & Philli, 2020. "Microglia-organized scar-free spinal cord repair in neonatal mice," Nature, Nature, vol. 587(7835), pages 613-618, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kun Rhee & Yanjie Wang & Johanna ten Hoeve & Linsey Stiles & Thao Thi Thu Nguyen & Xiangmei Zhang & Laurent Vergnes & Karen Reue & Orian Shirihai & Dean Bok & Xian-Jie Yang, 2022. "Ciliary neurotrophic factor-mediated neuroprotection involves enhanced glycolysis and anabolism in degenerating mouse retinas," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Xiangwei Li & Thomas Delerue & Ben Schöttker & Bernd Holleczek & Eva Grill & Annette Peters & Melanie Waldenberger & Barbara Thorand & Hermann Brenner, 2022. "Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    4. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Ulaganathan, Kandasamy & Goud, Sravanthi & Reddy, Madhavi & Kayalvili, Ulaganathan, 2017. "Genome engineering for breaking barriers in lignocellulosic bioethanol production," Renewable and Sustainable Energy Reviews, Elsevier, vol. 74(C), pages 1080-1107.
    6. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    7. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    9. Tianshi Feng & Xuemei Zhao & Ping Gu & Wah Yang & Cunchuan Wang & Qingyu Guo & Qiaoyun Long & Qing Liu & Ying Cheng & Jin Li & Cynthia Kwan Yui Cheung & Donghai Wu & Xinyu Kong & Yong Xu & Dewei Ye & , 2022. "Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Elisa Bellucci & Andrea Benazzo & Chunming Xu & Elena Bitocchi & Monica Rodriguez & Saleh Alseekh & Valerio Di Vittori & Tania Gioia & Kerstin Neumann & Gaia Cortinovis & Giulia Frascarelli & Ester Mu, 2023. "Selection and adaptive introgression guided the complex evolutionary history of the European common bean," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Jiayin Peng & Lili Han & Biao Liu & Jiawen Song & Yuang Wang & Kunpeng Wang & Qian Guo & XinYan Liu & Yu Li & Jujin Zhang & Wenqing Wu & Sheng Li & Xin Fu & Cheng-le Zhuang & Weikang Zhang & Shengbao , 2023. "Gli1 marks a sentinel muscle stem cell population for muscle regeneration," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Elisa Setten & Alessandra Castagna & Josué Manik Nava-Sedeño & Jonathan Weber & Roberta Carriero & Andreas Reppas & Valery Volk & Jessica Schmitz & Wilfried Gwinner & Haralampos Hatzikirou & Friedrich, 2022. "Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    13. Dafne Ibarra-Morales & Michael Rauer & Piergiuseppe Quarato & Leily Rabbani & Fides Zenk & Mariana Schulte-Sasse & Francesco Cardamone & Alejandro Gomez-Auli & Germano Cecere & Nicola Iovino, 2021. "Histone variant H2A.Z regulates zygotic genome activation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    14. Ryuki Shimada & Yuzuru Kato & Naoki Takeda & Sayoko Fujimura & Kei-ichiro Yasunaga & Shingo Usuki & Hitoshi Niwa & Kimi Araki & Kei-ichiro Ishiguro, 2023. "STRA8–RB interaction is required for timely entry of meiosis in mouse female germ cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Shuang Luo & Hao Jiang & Qingwei Li & Yingfei Qin & Shiping Yang & Jing Li & Lingli Xu & Yan Gou & Yafei Zhang & Fengjiang Liu & Xiao Ke & Qiang Zheng & Xun Sun, 2024. "An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    16. Maria J. Garcia-Leon & Cristina Liboni & Vincent Mittelheisser & Louis Bochler & Gautier Follain & Clarisse Mouriaux & Ignacio Busnelli & Annabel Larnicol & Florent Colin & Marina Peralta & Naël Osman, 2024. "Platelets favor the outgrowth of established metastases," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    17. Tingting Bo & Jie Li & Ganlu Hu & Ge Zhang & Wei Wang & Qian Lv & Shaoling Zhao & Junjie Ma & Meng Qin & Xiaohui Yao & Meiyun Wang & Guang-Zhong Wang & Zheng Wang, 2023. "Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Hao Chen & Frederick J. King & Bin Zhou & Yu Wang & Carter J. Canedy & Joel Hayashi & Yang Zhong & Max W. Chang & Lars Pache & Julian L. Wong & Yong Jia & John Joslin & Tao Jiang & Christopher Benner , 2024. "Drug target prediction through deep learning functional representation of gene signatures," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    19. Christina Koupourtidou & Veronika Schwarz & Hananeh Aliee & Simon Frerich & Judith Fischer-Sternjak & Riccardo Bocchi & Tatiana Simon-Ebert & Xianshu Bai & Swetlana Sirko & Frank Kirchhoff & Martin Di, 2024. "Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    20. Matthieu Dos Santos & Akansha M. Shah & Yichi Zhang & Svetlana Bezprozvannaya & Kenian Chen & Lin Xu & Weichun Lin & John R. McAnally & Rhonda Bassel-Duby & Ning Liu & Eric N. Olson, 2023. "Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40486-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.