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.
Date: 2017
Source: PLoS One   12: e0171898 (Journal)
Registered Authors: Chen, James K., Halluin, Caroline
Keywords: none
Microarrays: GEO:GSE72422
MeSH Terms:
  • Animal Fins/physiology*
  • Animals
  • Cell Proliferation/drug effects
  • Cell Proliferation/genetics
  • Epistasis, Genetic
  • Gene Expression Regulation/drug effects
  • Glucuronosyltransferase/genetics
  • Glucuronosyltransferase/metabolism
  • Glucuronosyltransferase/physiology*
  • Hyaluronic Acid/biosynthesis
  • Hyaluronic Acid/physiology*
  • Hymecromone/pharmacology
  • Regeneration/drug effects
  • Regeneration/genetics*
  • Signal Transduction/drug effects
  • Wound Healing/genetics
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed: 28207787 Full text @ PLoS One
Using 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.