Regeneration programs buffer genetic defects in animal development
- 1Morgridge Institute for Research, Madison, Wisconsin, United States of America
- 2Department of Cell and Regenerative Biology, University of Wisconsin--Madison, Madison, Wisconsin, United States of America
- 3Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, United States of America
Abstract
Regeneration programs enable animals to restore damaged or lost tissues, and the range of stimuli for these programs is incompletely understood. 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 fgf20a were mutagenized, and larvae homozygous for ENU-induced mutations were assessed for disruptions in fgf20a-directed reporter gene expression following fin fold amputation. One line was identified with heritable, elevated fgf20a:EGFP 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 fraser syndrome 1 (fras1) gene, mutated in patients with inherited skin disease. fras1 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 fras1 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.
Regeneration programs enable animals to restore damaged or lost tissues, but the stimuli that regulate these programs remain unclear. This study shows that mutations causing developmental defects activate regeneration responses that buffer the deleterious effects of congenital disease in zebrafish embryos.
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BibTeX
@article{ando2026regeneration,
title = {{Regeneration programs buffer genetic defects in animal development}},
author = {Kazunori Ando and Sushant Bangru and John Welsby and John D. Thompson and Kenneth D. Poss},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3004011},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004011},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Regeneration programs buffer genetic defects in animal development
AU - Kazunori Ando
AU - Sushant Bangru
AU - John Welsby
AU - John D. Thompson
AU - Kenneth D. Poss
PY - 2026
DA - 2026/09/21
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004011
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004011
AB - Regeneration programs enable animals to restore damaged or lost tissues, and the range of stimuli for these programs is incompletely understood. 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 fgf20a were mutagenized, and larvae homozygous for ENU-induced mutations were assessed for disruptions in fgf20a-directed reporter gene expression following fin fold amputation. One line was identified with heritable, elevated fgf20a:EGFP 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 fraser syndrome 1 (fras1) gene, mutated in patients with inherited skin disease. fras1 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 fras1 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. Regeneration programs enable animals to restore damaged or lost tissues, but the stimuli that regulate these programs remain unclear. This study shows that mutations causing developmental defects activate regeneration responses that buffer the deleterious effects of congenital disease in zebrafish embryos.
SN - 1545-7885
ER -