Model systems for regeneration: zebrafish

Abstract

Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies across tissues and between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well can help us develop strategies for tissue recovery in species with poor regenerative capacity (such as humans). The zebrafish (Danio rerio) is one of the most accessible vertebrate models to study regeneration. In this Primer, we highlight the tools available to study regeneration in the zebrafish, provide an overview of the mechanisms underlying regeneration in this system and discuss future perspectives for the field.

dnmt1function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye

“…By comparison, the mechanisms mediating RSC maintenance in vivo remain unknown. In studies of RSCs, the zebrafish has been advantageous given that it possesses a highly active RSC population and is tractable for genetic and pharmacological manipulations, transgenesis and in vivo imaging 19,20 .…”

“…By comparison, the mechanisms mediating RSC maintenance in vivo remain unknown. In studies of RSCs, the zebrafish has been advantageous given that it possesses a highly active RSC population and is tractable for genetic and pharmacological manipulations, transgenesis and in vivo imaging 19,20 .DNA methylation, a frequently studied epigenetic modification, is the process through which a methyl group is added to the fifth carbon of cytosine nucleotides and is commonly found at CpG dinucleotide sequences 21 . Members of the family of DNA methyltransferase (Dnmt) enzymes 22,23 catalyze this epigenetic modification.…”

A role for theMEGF6gene in predisposition to osteoporosis

“…This phenotype may be due to factors unique to the teleost lineage, including sex differences and compensatory growth mechanisms. Zebrafish grow in size throughout their lifetime and have prodigious regenerative capacities (46,47), which may contribute to the mild adult phenotype and the observed phenotypic differences between males and females. Further characterization of the zebrafish megf6a;6b mutant phenotype in aged adults and generation of zebrafish with the human disease allele (48) will provide insight into the genetic mechanisms of osteoporosis and may yield new targets for therapeutic intervention.…”

Morphine alleviates pain after heart cryoinjury in zebrafish without impeding regeneration

“…The adult zebrafish has become a popular animal model to study vertebrate regeneration, including heart regeneration. Current methodologies inducing the injury of the heart tissue include resection, cryoinjury, genetic ablation and hypoxia/reoxygenation (González-Rosa et al, 2017; Marques et al, 2019). The cryoprobe injury model is based on rapid freezing-and-thawing of the heart tissue, resulting in the cell death of about 20% of cardiomyocytes (CM) of the ventricular wall (Figure 1 A, B) (Chablais and Jazwinska, 2012; Chablais et al, 2011; González-Rosa and Mercader, 2012).…”

“…This procedure causes local damage to all cardiac cell types and leads to a transient fibrotic tissue deposition reminiscent of the fibrotic scar formed in mammals after myocardial infarction (Kikuchi, 2014). In general, within 30 to 60 days after injury the heart is fully regenerated (González-Rosa et al, 2017; Marques et al, 2019). Although the cryoinjury method has been widely used to induce cardiac injury in sedated zebrafish using tricaine methanesulfonate, analgesics were never tested during this procedure.…”