Roles of retinoic acid in the regeneration of the zebrafish larval and adult caudal fin

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Teleost fish are able to regenerate injured organs, such as the fins and heart. In the zebrafish amputated fins regenerate through epimorphic regeneration, in which a blastema, a mass of undifferentiated cells, forms to reconstitute the lost structures. Despite the recent identification of several genes required for the regeneration process, the current knowledge of the constituents and interactions of the underlying regulatory gene network remains very patchy. Retinoic acid (RA) controls the activity of genes required for a vast number of developmental processes. We have found compelling support for the hypothesis that RA signaling is indispensable for both larval and adult fin regeneration. To be able to manipulate RA signaling during adult fin regeneration, we have established a transgenic line which allows the controlled inactivation of RA signaling. Using this and other tools, we propose to examine how and at which stages RA interferes with the regenerative processes in larvae and adults. We will study cell migration and proliferation under conditions in which the RA pathway is inactive and will examine its genetic interactions with known signaling pathways. In addition, we will investigate the function of a microRNA that targets the aldh1a2 gene, required for RA synthesis, and is known to be expressed in regenerating fins. Our studies are likely to throw light on differences between these processes in larval and adult organs and could help to understand why regenerative abilities are more restricted in adult vertebrates.