PUBLICATION
Hyaluronic acid synthesis is required for zebrafish tail fin regeneration
- Authors
- Ouyang, X., Panetta, N.J., Talbott, M.D., Payumo, A.Y., Halluin, C., Longaker, M.T., Chen, J.K.
- ID
- ZDB-PUB-170217-1
- Date
- 2017
- Source
- PLoS One 12: e0171898 (Journal)
- Registered Authors
- Chen, James K., Halluin, Caroline
- Keywords
- none
- Datasets
- 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
Citation
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.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping