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

硬骨鱼能够再生受伤的器官，如鳍和心脏。在斑马鱼中，断肢的鳍通过表型再生进行再生，在表型再生中，形成一个芽基，一团未分化的细胞，以重建失去的结构。尽管最近鉴定了再生过程所需的几个基因，但目前对潜在调控基因网络的组成和相互作用的了解仍然非常零散。视黄酸（RA）控制着大量发育过程所需的基因活性。我们已经发现令人信服的支持的假设，RA信号是不可或缺的幼虫和成人鳍再生。为了能够在成体鳍再生过程中操纵RA信号，我们已经建立了一个转基因系，它允许RA信号的受控失活。使用这个和其他工具，我们建议研究如何以及在哪个阶段RA干扰幼虫和成虫的再生过程。我们将研究细胞迁移和增殖的条件下，RA途径是不活跃的，并将检查其与已知的信号传导途径的遗传相互作用。此外，我们将研究一种靶向RA合成所需的aldh1a2基因的microRNA的功能，该基因已知在再生鳍中表达。我们的研究可能会揭示幼虫和成年器官中这些过程之间的差异，并有助于理解为什么再生能力在成年脊椎动物中受到更多限制。

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.