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

视黄酸在斑马鱼幼体和成体尾鳍再生中的作用

基本信息

批准号：
145471412
负责人：
Professor Dr. Gerrit Begemann
金额：
--
依托单位：
Lehrstuhl für Tierphysiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/145471412?language=en
关键词：
Roles retinoic acid regeneration zebrafish

项目摘要

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.

硬骨鱼能够再生受损的器官，如鳍和心脏。在斑马鱼中，截肢的鳍通过表形再生再生，在表型再生中，胚泡--一群未分化的细胞--形成，以重建丢失的结构。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参差不齐。维甲酸(RA)控制着大量发育过程所需基因的活性。我们发现，RA信号对幼体和成体鳍的再生都是不可或缺的，这一假设得到了令人信服的支持。为了能够在成体鳍再生过程中操纵RA信号，我们建立了一个转基因株系，它允许RA信号的受控失活。使用这一工具和其他工具，我们建议检查RA如何以及在哪些阶段干扰幼虫和成虫的再生过程。我们将研究在RA途径不活跃的条件下细胞的迁移和增殖，并将检查其与已知信号通路的遗传相互作用。此外，我们还将研究针对aldh1a2基因的microRNA的功能，该基因是RA合成所必需的，已知在再生FINS中表达。我们的研究可能有助于阐明幼虫和成体器官中这些过程的差异，并有助于理解为什么成年脊椎动物的再生能力更有限。