Progenitor-derived Glia Are Required for Spinal Cord Regeneration in Zebrafish

Overview

Journal Development

Specialty Biology

Date 2023 May 22

PMID 37213080

Authors

Lili Zhou

Anthony R McAdow

Hunter Yamada

Brooke Burris

Dana Klatt Shaw

Kelsey Oonk

Kenneth D Poss

Mayssa H Mokalled

Affiliations

Soon will be listed here.

Abstract

Unlike mammals, adult zebrafish undergo spontaneous recovery after major spinal cord injury. Whereas reactive gliosis presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish elicit pro-regenerative bridging functions after injury. Here, we perform genetic lineage tracing, assessment of regulatory sequences and inducible cell ablation to define mechanisms that direct the molecular and cellular responses of glial cells after spinal cord injury in adult zebrafish. Using a newly generated CreERT2 transgenic line, we show that the cells directing expression of the bridging glial marker ctgfa give rise to regenerating glia after injury, with negligible contribution to either neuronal or oligodendrocyte lineages. A 1 kb sequence upstream of the ctgfa gene was sufficient to direct expression in early bridging glia after injury. Finally, ablation of ctgfa-expressing cells using a transgenic nitroreductase strategy impaired glial bridging and recovery of swim behavior after injury. This study identifies key regulatory features, cellular progeny, and requirements of glial cells during innate spinal cord regeneration.

Citing Articles

Protocol for whole-mount preparation, clearing, and visualization of the adult zebrafish spinal cord structures.

Rebocho da Costa M, Ribeiro A, Quiteria R, Neves-Silva D, Saude L STAR Protoc. 2024; 5(4):103491.

PMID: 39656590 PMC: 11683226. DOI: 10.1016/j.xpro.2024.103491.

Retinoic acid, an essential component of the roof plate organizer, promotes the spatiotemporal segregation of dorsal neural fates.

Rekler D, Ofek S, Kagan S, Friedlander G, Kalcheim C Development. 2024; 151(19).

PMID: 39250350 PMC: 11463963. DOI: 10.1242/dev.202973.

Astrocyte-Neuron Interactions in Spinal Cord Injury.

Reyes C, Mokalled M Adv Neurobiol. 2024; 39:213-231.

PMID: 39190077 PMC: 11684398. DOI: 10.1007/978-3-031-64839-7_9.

Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair.

Saraswathy V, Zhou L, Mokalled M Nat Commun. 2024; 15(1):6808.

PMID: 39147780 PMC: 11327264. DOI: 10.1038/s41467-024-50628-y.

Effect of Voltage-Gated K Channel Inhibition by 4-aminopyridine in Spinal Cord Injury Recovery in Zebrafish.

Hoffman P, Mruk K bioRxiv. 2024; .

PMID: 39071260 PMC: 11275812. DOI: 10.1101/2024.07.15.603582.

References

Wu W, You R, Cheng C, Lee M, Lin T, Hu C . Snail collaborates with EGR-1 and SP-1 to directly activate transcription of MMP 9 and ZEB1. Sci Rep. 2017; 7(1):17753. PMC: 5736704. DOI: 10.1038/s41598-017-18101-7. View

Curado S, Stainier D, Anderson R . Nitroreductase-mediated cell/tissue ablation in zebrafish: a spatially and temporally controlled ablation method with applications in developmental and regeneration studies. Nat Protoc. 2008; 3(6):948-54. PMC: 2705989. DOI: 10.1038/nprot.2008.58. View

Choi H, Schwarzkopf M, Fornace M, Acharya A, Artavanis G, Stegmaier J . Third-generation hybridization chain reaction: multiplexed, quantitative, sensitive, versatile, robust. Development. 2018; 145(12). PMC: 6031405. DOI: 10.1242/dev.165753. View

Mokalled M, Patra C, Dickson A, Endo T, Stainier D, Poss K . Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish. Science. 2016; 354(6312):630-634. PMC: 5114142. DOI: 10.1126/science.aaf2679. View

Grimpe B, Silver J . A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. J Neurosci. 2004; 24(6):1393-7. PMC: 6730336. DOI: 10.1523/JNEUROSCI.4986-03.2004. View

Dongre A, Weinberg R . New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2018; 20(2):69-84. DOI: 10.1038/s41580-018-0080-4. View

Wilson M, Weinberg R, Lees J, Guen V . Emerging Mechanisms by which EMT Programs Control Stemness. Trends Cancer. 2020; 6(9):775-780. DOI: 10.1016/j.trecan.2020.03.011. View

Saraswathy V, Zhou L, McAdow A, Burris B, Dogra D, Reischauer S . Myostatin is a negative regulator of adult neurogenesis after spinal cord injury in zebrafish. Cell Rep. 2022; 41(8):111705. PMC: 9742758. DOI: 10.1016/j.celrep.2022.111705. View

Silver J, Miller J . Regeneration beyond the glial scar. Nat Rev Neurosci. 2004; 5(2):146-56. DOI: 10.1038/nrn1326. View

10.

Dias D, Goritz C . Fibrotic scarring following lesions to the central nervous system. Matrix Biol. 2018; 68-69:561-570. DOI: 10.1016/j.matbio.2018.02.009. View

11.

Zhao B, Ye X, Yu J, Li L, Li W, Li S . TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008; 22(14):1962-71. PMC: 2492741. DOI: 10.1101/gad.1664408. View

12.

Reimer M, Sorensen I, Kuscha V, Frank R, Liu C, Becker C . Motor neuron regeneration in adult zebrafish. J Neurosci. 2008; 28(34):8510-6. PMC: 6671064. DOI: 10.1523/JNEUROSCI.1189-08.2008. View

13.

Sofroniew M . Dissecting spinal cord regeneration. Nature. 2018; 557(7705):343-350. DOI: 10.1038/s41586-018-0068-4. View

14.

Dervan A, Roberts B . Reaction of spinal cord central canal cells to cord transection and their contribution to cord regeneration. J Comp Neurol. 2003; 458(3):293-306. DOI: 10.1002/cne.10594. View

15.

Han W, Zhang Y, Niu C, Guo J, Li J, Wei X . BTB and CNC homology 1 (Bach1) promotes human ovarian cancer cell metastasis by HMGA2-mediated epithelial-mesenchymal transition. Cancer Lett. 2019; 445:45-56. DOI: 10.1016/j.canlet.2019.01.003. View

16.

Briona L, Poulain F, Mosimann C, Dorsky R . Wnt/ß-catenin signaling is required for radial glial neurogenesis following spinal cord injury. Dev Biol. 2015; 403(1):15-21. PMC: 4469497. DOI: 10.1016/j.ydbio.2015.03.025. View

17.

Mosimann C, Kaufman C, Li P, Pugach E, Tamplin O, Zon L . Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafish. Development. 2010; 138(1):169-77. PMC: 2998170. DOI: 10.1242/dev.059345. View

18.

Shaw D, Saraswathy V, Zhou L, McAdow A, Burris B, Butka E . Localized EMT reprograms glial progenitors to promote spinal cord repair. Dev Cell. 2021; 56(5):613-626.e7. PMC: 8044706. DOI: 10.1016/j.devcel.2021.01.017. View

19.

Vassilev A, Kaneko K, Shu H, Zhao Y, DePamphilis M . TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm. Genes Dev. 2001; 15(10):1229-41. PMC: 313800. DOI: 10.1101/gad.888601. View

20.

Grotendorst G, Duncan M . Individual domains of connective tissue growth factor regulate fibroblast proliferation and myofibroblast differentiation. FASEB J. 2005; 19(7):729-38. DOI: 10.1096/fj.04-3217com. View