Open AccessHyaluronic acid synthesis is required for zebrafish tail fin regeneration
Author(s) -
Xiaohu Ouyang,
Nicholas J. Panetta,
Maya Talbott,
Alexander Y. Payumo,
Caroline Halluin,
Michael T. Longaker,
James Chen
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0171898
Subject(s) - blastema , hyaluronan synthase , zebrafish , microbiology and biotechnology , biology , regeneration (biology) , hyaluronic acid , gsk 3 , wound healing , fibroblast growth factor , epithelium , kinase , extracellular matrix , anatomy , genetics , gene , receptor
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.