|ZFIN ID: ZDB-PUB-170217-1|
Hyaluronic acid synthesis is required for zebrafish tail fin regeneration
Ouyang, X., Panetta, N.J., Talbott, M.D., Payumo, A.Y., Halluin, C., Longaker, M.T., Chen, J.K.
|Source:||PLoS One 12: e0171898 (Journal)|
|Registered Authors:||Chen, James K., Halluin, Caroline|
|PubMed:||28207787 Full text @ PLoS One|
Ouyang, X., Panetta, N.J., Talbott, M.D., Payumo, A.Y., Halluin, C., Longaker, M.T., Chen, J.K. (2017) Hyaluronic acid synthesis is required for zebrafish tail fin regeneration. PLoS One. 12:e0171898.
ABSTRACTUsing genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-ß signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impairs tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation. In addition, 4-MU reduces the expression of genes associated with wound epithelium and blastema function. Treatment with glycogen synthase kinase 3 inhibitors rescues 4-MU-induced defects in cell proliferation and tail regeneration, while restoring a subset of wound epithelium and blastema markers. Our findings demonstrate a role for HA biosynthesis in zebrafish tail regeneration and delineate its epistatic relationships with other regenerative processes.