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
The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
Curr Mol Med. 2017;17(9):627-636. doi: 10.2174/1566524018666180308113909.
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.
Whole-mount in situ hybridization and embryo immunostaining were performed.
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.
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.
四又二分之一LIM结构域蛋白1（FHL1）突变与人类肌病相关。然而，该蛋白在骨骼发育中的功能仍不清楚。
进行整体原位杂交和胚胎免疫染色。
斑马鱼Fhl1A是人类FHL1的同源物。我们发现敲低fhl1A会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。我们还证明敲低fhl1A会减少卫星细胞的数量。卫星细胞数量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。我们还证明fhl1A表达和视黄酸（RA）信号传导导致相似的骨骼肌发育表型。此外，用外源性RA处理时，骨骼肌中内源性fhl1A表达增强。用DEAB（一种抑制视黄醛脱氢酶活性的RA信号传导抑制剂）处理时，fhl1A表达下调。
fhl1A在调节卫星细胞数量和骨骼肌发育中起激活剂作用。fhl1A在骨骼肌生成中的作用受RA信号传导调节。
