Gene expression and functional analysis of zebrafish larval fin fold regeneration

Teleost fish have a remarkable ability to regenerate their body parts compared to many higher vertebrates including humans. To facilitate molecular and genetic approaches for regeneration, we previously established an assay using the fin fold of zebrafish larvae. Here, we performed transcriptional profiling and identified genes differentially controlled during regeneration. From up-regulated transcripts, we identified a number of genes with localized expressions. Strikingly, all identified genes were also induced in the regenerating adult fin, which has a different tissue origin from the larval fin fold. This result supports the commonality of regeneration irrespective of tissue type and stage. Importantly, our analysis suggested that the regenerating tissue had many more compartments than generally assumed ones, the blastema and wound epidermis. By pharmacological and genetic approaches, we further evaluated functional involvement of induced molecules. Inhibition of Mmp9 function impaired proper morphological restoration without disturbing cell proliferation. Genetic mutations of blastema genes, hspa9 and smarca4, disrupted the fin fold regeneration by impairing the blastema cell proliferation. Thus, our results demonstrate that the regeneration model of juvenile zebrafish offers a powerful assay to dissect the regeneration processes.