The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor γ: evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid

Htoo Aung Wai, Koichi Kawakami, Hironori Wada, Ferenc Müller, Ann Beatrice Vernallis, Geoffrey Brown, William Eustace Basil Johnson*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)-RARα, RARβ, and RARγ-is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.

Original languageEnglish
Pages (from-to)507-519
Number of pages13
JournalStem cells and development
Volume24
Issue number4
Early online date10 Nov 2014
DOIs
Publication statusPublished - 13 Feb 2015

Bibliographical note

© Htoo Aung Wai et al. 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License Attribution-Non-Commercial Share Alike (http://creativecommons.org/licenses/by-nc-sa/4.0/).

Funding: Charles Wallace Trust; European Union’s Seventh Framework Programme FP7/2007–2013/under REA grant 315902.

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