Dynamic cell interactions allow spinal cord regeneration in zebrafish

Becker, Thomas; Becker, Catherina G.

doi:10.1016/j.cophys.2020.01.009

Cited by 11 publications

(10 citation statements)

References 63 publications

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“…However, tgfb1a and tgfb3 are also expressed by other cell types [ 3 ] and may interact with cell types other than neutrophils, such as astrocytes [ 36 ] or the neurons directly [ 34 , 37 ]. Since the interactions of a number of different cell types, such as immune, and neural cell types, but non-neural cells, such as fibroblasts and keratinocytes, are highly complex in the spinal injury site [ 2 ], future research will have to dissect influences of Tgf-β signalling on spatio-temporal interactions of these cell types.…”

Section: Discussionmentioning

confidence: 99%

“…Zebrafish, in contrast to mammals, functionally regenerate axonal connections across the injury site after spinal cord injury. Prolonged inflammation is detrimental to recovery from a spinal injury in mammals, but in zebrafish, pro-inflammatory cytokines are rapidly down-regulated and the immune response generally promotes regeneration [ 1 , 2 ]. Specifically, previous work has shown that the presence of blood-derived macrophages is crucial for axonal reconnection in the injured larval spinal cord and recovery from paralysis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury

et al. 2021

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Zebrafish exhibit robust regeneration following spinal cord injury, promoted by macrophages that control post-injury inflammation. However, the mechanistic basis of how macrophages regulate regeneration is poorly understood. To address this gap in understanding, we conducted a rapid in vivo phenotypic screen for macrophage-related genes that promote regeneration after spinal injury. We used acute injection of synthetic RNA Oligo CRISPR guide RNAs (sCrRNAs) that were pre-screened for high activity in vivo. Pre-screening of over 350 sCrRNAs allowed us to rapidly identify highly active sCrRNAs (up to half, abbreviated as haCRs) and to effectively target 30 potentially macrophage-related genes. Disruption of 10 of these genes impaired axonal regeneration following spinal cord injury. We selected 5 genes for further analysis and generated stable mutants using haCRs. Four of these mutants (tgfb1a, tgfb3, tnfa, sparc) retained the acute haCR phenotype, validating the approach. Mechanistically, tgfb1a haCR-injected and stable mutant zebrafish fail to resolve post-injury inflammation, indicated by prolonged presence of neutrophils and increased levels of il1b expression. Inhibition of Il-1β rescues the impaired axon regeneration in the tgfb1a mutant. Hence, our rapid and scalable screening approach has identified functional regulators of spinal cord regeneration, but can be applied to any biological function of interest.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury

et al. 2021

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“…After a spinal cord injury, neurons die and they, or their function need to be replaced. In zebrafish, regeneration occurs through complex interactions between different cell types and is orchestrated by a range of signals, as reviewed in [10]. Amongst the cells involved in this process, immune cells are key players.…”

Section: Cellsmentioning

confidence: 99%

Neural circuit reorganisation after spinal cord injury in zebrafish

El-Daher

Becker

2020

Current Opinion in Genetics & Development

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Spinal cord injuries disrupt signalling from the brain leading to loss of limb, locomotion, sexual and bladder function, usually irreversible in humans. In zebrafish, recovery of function occurs in a few days for larvae or a few weeks for adults due to regrowth of axons and de novo neurogenesis. Together with its genetic amenability and optical clarity, this makes zebrafish a powerful animal model to study circuit reorganisation after spinal cord injuries. With the fast evolution of techniques, we can forecast significative improvements of our knowledge of the mechanisms leading to successful or failed recovery of spinal cord function. We review here the present knowledge on the subject, the new technological approaches and we propose future directions of research.

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“…This is driven by pro-regenerative gene expression (e.g. col12a1a/b and tenascin-c ), interactions with other cell types such as Schwann cells, and additional environmental cues 180 , 182 , 184 , 188 – 190 . Zebrafish glial bridging shares clear morphological and functional similarities with the bridging observed during mammalian peripheral nerve regeneration (which occurs to a much greater extent than mammalian CNS regeneration) 183 , 191 – 193 , indicating that this common process may be manipulated in the human for therapeutic benefit.…”

Section: Introductionmentioning

confidence: 99%

Hippo-Yap/Taz signalling in zebrafish regeneration

Riley

Feng

2022

npj Regen Med

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The extent of tissue regeneration varies widely between species. Mammals have a limited regenerative capacity whilst lower vertebrates such as the zebrafish (Danio rerio), a freshwater teleost, can robustly regenerate a range of tissues, including the spinal cord, heart, and fin. The molecular and cellular basis of this altered response is one of intense investigation. In this review, we summarise the current understanding of the association between zebrafish regeneration and Hippo pathway function, a phosphorylation cascade that regulates cell proliferation, mechanotransduction, stem cell fate, and tumorigenesis, amongst others. We also compare this function to Hippo pathway activity in the regenerative response of other species. We find that the Hippo pathway effectors Yap/Taz facilitate zebrafish regeneration and that this appears to be latent in mammals, suggesting that therapeutically promoting precise and temporal YAP/TAZ signalling in humans may enhance regeneration and hence reduce morbidity.

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Dynamic cell interactions allow spinal cord regeneration in zebrafish

Cited by 11 publications

References 63 publications

CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury

CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury

Neural circuit reorganisation after spinal cord injury in zebrafish

Hippo-Yap/Taz signalling in zebrafish regeneration

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