Title:Role of Zebrafish fhl1A in Satellite Cell and Skeletal Muscle Development
VOLUME: 17 ISSUE: 9
Author(s):F. Chen, W. Yuan, X. Mo, J. Zhuang, Y. Wang, J. Chen, Z. Jiang, X. Zhu, Q. Zeng, Y. Wan, F. Li, Y. Shi, L. Cao, X. Fan, S. Luo, X. Ye, Y. Chen, G. Dai, J. Gao, X. Wang, H. Xie*, P. Zhu*, Y. Li* and X. Wu*
Affiliation:The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Lab of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081
Keywords:fhl1A, satellite cells, skeletal muscle, development, zebrafish, myogenesis.
Abstract: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.
