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Here, we used zebrafish, a vertebrate species with exceptional regenerative capacity, to identify chemically induced mutations that alter regeneration-associated gene activation. Transgenic zebrafish with a permissive promoter and EGFP cassette inserted in the vicinity of the pro-regenerative factor gene\n                    <jats:italic>fgf20a<\/jats:italic>\n                    were mutagenized, and larvae homozygous for ENU-induced mutations were assessed for disruptions in\n                    <jats:italic>fgf20a<\/jats:italic>\n                    -directed reporter gene expression following fin fold amputation. One line was identified with heritable, elevated\n                    <jats:italic>fgf20a<\/jats:italic>\n                    :\n                    <jats:italic>EGFP<\/jats:italic>\n                    presence in the absence of experimental injury, localized to regions of fin fold tissue undergoing degeneration. Whole-genome sequencing identified a mutation within exon 72 of the\n                    <jats:italic>fraser syndrome 1<\/jats:italic>\n                    (\n                    <jats:italic>fras1<\/jats:italic>\n                    ) gene, mutated in patients with inherited skin disease.\n                    <jats:italic>fras1<\/jats:italic>\n                    mutant larvae spontaneously displayed broader signatures of regeneration, and zebrafish crispants for homologs of other genes mutated in human developmental diseases also displayed regeneration-associated gene expression in regions of dysmorphology. Tempering Fgf signaling by transgenic expression of a dominant-negative Fgf receptor in\n                    <jats:italic>fras1<\/jats:italic>\n                    mutants exacerbated the disease phenotype. Our findings provide evidence that regeneration programs are harnessed in response to developmental defects caused by genetic mutations, potentially buffering deleterious phenotypes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3004011","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:02:47Z","timestamp":1790013767000},"page":"e3004011","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regeneration programs buffer genetic defects in animal development"],"prefix":"10.1371","volume":"24","author":[{"given":"Kazunori","family":"Ando","sequence":"first","affiliation":[{"name":"Morgridge Institute for Research","place":["Madison, Wisconsin, United States of America"]},{"name":"University of Wisconsin--Madison","place":["Madison, Wisconsin, United States of America"],"department":["Department of Cell and Regenerative 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