Role of Zebrafish fhl1A in Satellite Cell and Skeletal Muscle Development.
Role of Zebrafish fhl1A in Satellite Cell and Skeletal Muscle Development.
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斑马鱼 fhl1A 在卫星细胞和骨骼肌发育中的作用
DOI：
10.2174/1566524018666180308113909
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发表时间：
2017
影响因子：
2.5
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Chen F;Yuan W;Mo X;Zhuang J;Wang Y;Chen J;Jiang Z;Zhu X;Zeng Q;Wan Y;Li F;Shi Y;Cao L;Fan X;Luo S;Ye X;Chen Y;Dai G;Gao J;Wang X;Xie H;Zhu P;Li Y;Wu X
背景：四个半LIM结构域蛋白1（FHL1）突变与人类肌病相关。然而，这种蛋白质在骨骼发育中的功能仍不清楚。方法：采用整体原位杂交和胚胎免疫组化技术。结果：斑马鱼Fhl1A与人FHL1同源。我们发现，fhl1A敲低导致骨骼肌发育缺陷，而注射fhl1A mRNA在很大程度上恢复了这些fhl1A morphants的肌肉发育。我们还证明了fhllA敲低减少了卫星细胞的数量。卫星细胞的减少和骨骼肌异常的出现与myoD、pax7、mef2ca和skMLCK基因表达的改变有关。我们还表明，fhl1A的表达和视黄酸（RA）信号引起类似的骨骼肌发育表型。此外，当用外源性RA处理时，骨骼肌中的内源性fhllA表达是稳健的。当用DEAB（一种抑制视黄醇脱氢酶活性的RA信号传导抑制剂）处理时，fhl1A被下调。结论：fhl1A作为一种激活剂参与了骨骼肌卫星细胞数量的调节和骨骼肌的发育。fhllA在骨骼肌发生中的作用受RA信号转导调节。
Background: Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. Methods: Whole-mount in situ hybridization and embryo immunostaining were performed. Results: Zebrafish Fhl1A is the homologue of human FHL1. We showed that fhl1A knockdown causes defective skeletal muscle development, while injection with fhl1A mRNA largely recovered the muscle development in these fhl1A morphants. We also demonstrated that fhl1A knockdown decreases the number of satellite cells. This decrease in satellite cells and the emergence of skeletal muscle abnormalities were associated with alterations in the gene expression of myoD, pax7, mef2ca and skMLCK. We also demonstrated that fhl1A expression and retinoic acid (RA) signalling caused similar skeletal muscle development phenotypes. Moreover, when treated with exogenous RA, endogenous fhl1A expression in skeletal muscles was robust. When treated with DEAB, an RA signalling inhibitor which inhibits the activity of retinaldehyde dehydrogenase, fhl1A was downregulated. Conclusion: fhl1A functions as an activator in regulating the number of satellite cells and in skeletal muscle development. The role of fhl1A in skeletal myogenesis is regulated by RA signaling.