Cartilage development requires the function of Estrogen-related receptor alpha that directly regulates sox9 expression in zebrafish
Cartilage development requires the function of Estrogen-related receptor alpha that directly regulates sox9 expression in zebrafish
复制标题
DOI：
10.1038/srep18011
复制
发表时间：
2015-12-10
影响因子：
4.6
通讯作者：
Park, Raekil
中科院分区：
文献类型：
--
作者：
Kim, Yong-Il;Lee, Joon No;Park, Raekil
雌激素相关受体α（ESRRa）调节许多细胞过程，包括骨骼和肌肉的发育。然而，关于其参与软骨发育的直接证据仍然难以捉摸。在这份报告中，我们建立了在斑马鱼胚胎发育过程中的软骨发育Esrra在体内的作用。基因表达分析表明，esrra在发育中的咽弓中表达，其中软骨发育所必需的基因也表达。功能缺失分析表明，esrra的敲低损害了包括sox9、col2a1、sox5、sox6、runx2和col10a1在内的基因的表达，从而诱导咽弓软骨的异常形成。重要的是，我们确定了推定的ESRRa结合元件在上游地区的sox9 ESRRa可以直接结合，表明Esrra可能直接调节sox9的表达。因此，sox9的异位表达挽救了由esrra敲低诱导的软骨缺陷形成。总之，我们的研究结果首次表明ESRRa通过调节脊椎动物发育过程中sox9的表达对软骨发育至关重要。
Estrogen-related receptor alpha (ESRRa) regulates a number of cellular processes including development of bone and muscles. However, direct evidence regarding its involvement in cartilage development remains elusive. In this report, we establish an in vivo role of Esrra in cartilage development during embryogenesis in zebrafish. Gene expression analysis indicates that esrra is expressed in developing pharyngeal arches where genes necessary for cartilage development are also expressed. Loss of function analysis shows that knockdown of esrra impairs expression of genes including sox9, col2a1, sox5, sox6, runx2 and col10a1 thus induces abnormally formed cartilage in pharyngeal arches. Importantly, we identify putative ESRRa binding elements in upstream regions of sox9 to which ESRRa can directly bind, indicating that Esrra may directly regulate sox9 expression. Accordingly, ectopic expression of sox9 rescues defective formation of cartilage induced by the knockdown of esrra. Taken together, our results indicate for the first time that ESRRa is essential for cartilage development by regulating sox9 expression during vertebrate development.