{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316679/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Danio rerio"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316679"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A Gata4–Loxl2 Axis Controls ECM Remodeling to Enable Scar-Free Spinal-Cord Regeneration in Zebrafish","description":"Spinal-cord injury in mammals causes permanent loss of sensory and motor function due to scar formation obstructing axon regrowth. In contrast, zebrafish fully regenerate their spinal cord without lasting fibrosis. Here, we identify the transcription factor GATA4 as a key regulator of regeneration. After injury, Gata4 is primarily upregulated in dorsal ependymo-radial glial cells (ERGs). GATA4 preserves glial identity and orchestrates regenerative extracellular matrix (ECM) remodeling. GATA4 loss biases ERGs toward a fibroblast-like state with upregulated Loxl2, a collagen cross-linking enzyme, and can also increase Loxl2 in surrounding non-glial cells. Excess Loxl2 activity promotes pathological crosslinking and formation of a rigid, fibrotic matrix impairing glial and axonal bridging across the lesion, greatly reducing motor recovery. Pharmacological inhibition of Loxl2 in gata4 mutants substantially rescues ECM organization, tissue bridging, and functional recovery. Injury-induced Gata4 activation depends on a short hypoxia-responsive enhancer and is driven, at least in part, by Hif1a signaling. We identify the Gata4–Loxl2 axis as a central regulator of and potential therapeutic target for scar-free spinal-cord repair.","dates":{"publication":"2026/08/11"},"accession":"GSE316679","cross_references":{"GSM":["GSM9458135"],"GPL":["29008"],"GSE":["316679"],"taxon":["Danio rerio"]}}