摘要
背景:四分之一LIM结构域蛋白1(FHL1)突变与人类肌病有关。然而,这种蛋白质在骨骼发育中的功能仍不清楚。 方法:进行全身原位杂交和胚胎免疫染色。 结果:斑马鱼Fhl1A是人FHL1的同源物。我们发现,fhl1A敲除引起骨骼肌发育缺陷,而注射fhl1A mRNA大大恢复了这些fhl1A morphants的肌肉发育。我们还证明fhl1A敲除减少了卫星细胞的数量。卫星细胞的这种减少和骨骼肌异常的出现与myoD,pax7,mef2ca和skMLCK的基因表达的改变相关。我们还证明fhl1A表达和视黄酸(RA)信号引起类似的骨骼肌发育表型。而且,当用外源RA处理时,骨骼肌中的内源性fhl1A表达是强有力的。当用抑制视黄醛脱氢酶活性的RA信号抑制剂DEAB处理时,fhl1A下调。 结论:fhl1A在调节卫星细胞数量和骨骼肌发育中起着激活剂的作用。 fhl1A在骨骼肌发生中的作用受RA信号调节。
关键词: fhl1A,卫星细胞,骨骼肌,发育,斑马鱼,肌生成。
Current Molecular Medicine
Title:Role of Zebrafish fhl1A in Satellite Cell and Skeletal Muscle Development
Volume: 17 Issue: 9
关键词: fhl1A,卫星细胞,骨骼肌,发育,斑马鱼,肌生成。
摘要: 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.
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Cite this article as:
Role of Zebrafish fhl1A in Satellite Cell and Skeletal Muscle Development, Current Molecular Medicine 2017; 17 (9) . https://dx.doi.org/10.2174/1566524018666180308113909
DOI https://dx.doi.org/10.2174/1566524018666180308113909 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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