ArticlePLoS genetics2021
CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Disrupting fzd9b in Zebrafish Recapitulates Stress- and Anxiety-Like Behaviours Relevant to Williams Syndrome.Molecular neurobiology · 2026Article
- A Preliminary Zebrafish Model ofGenes · 2026Article
- The microglia-derived protein Sema4ab attenuates regenerative neurogenesis after spinal cord injury in zebrafish.PLoS biology · 2026Article
- A reparative neutrophil subpopulation accelerates spinal cord regeneration in zebrafish by controlling macrophage inflammation via Il-4.Journal of neuroinflammation · 2026Article
- In vivo screen reveals specific roles of Hippo pathway components in development and regeneration.Life science alliance · 2026Article
- ift140 -Deficient Zebrafish as a Model for Kidney Cystogenesis and an F0-Based Screen for Genetic Modifiers of Kidney Cysts.Journal of the American Society of Nephrology : JASN · 2026Article
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- rbfox1 LoF mutants show disrupted bdnf/trkb2 and crhb/nr3c2 expression and increased cortisol levels during development coupled with signs of allostatic overload in adulthood.Translational psychiatry · 2025Article
- TGF-beta coordinates changes in Keratin gene expression during complex tissue regeneration.Scientific reports · 2025Article
- Effects of age on the response to spinal cord injury: optimizing the larval zebrafish model.Developmental biology · 2025Article
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- Activity-driven myelin sheath growth is mediated by mGluR5.Nature neuroscience · 2025Article
- A zebrafish model of acmsd deficiency does not support a prominent role for ACMSD in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Blueprints for healing: central nervous system regeneration in zebrafish and neonatal mice.BMC biology · 2025Review
- Correction: Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.Life science alliance · 2025Article
- ThemBio · 2025Article
- Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae.Life science alliance · 2025Article
- Interleukin-34 orchestrates bone formation through its binding to bone morphogenic proteins.Theranostics · 2025Article
- Hot topics in Cellular Neuropathology IV-targeting neurological diseases by gene therapy approaches.Frontiers in cellular neuroscience · 2025Article
- Modeling traumatic brain and neural injuries: insights from zebrafish.Frontiers in molecular neuroscience · 2025Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.