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The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor (RAR) γ: evidence that RARγ functions to maintain stem/progenitor cells in the absence of retinoic acid
Wai, H.A., Wada, H., Kawakami, K., Müller, F., Vernallis, A.B., Brown, G., Johnson, W.E. (2015) The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor (RAR) γ: evidence that RARγ functions to maintain stem/progenitor cells in the absence of retinoic acid. Stem cells and development. 24(4):507-19.
Retinoic acid (RA) signalling is important to normal development. However, the function of the different retinoic acid receptors (RAR), 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 hoxb 13a expression and less clear alterations in hoxc 11a 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 wash out or by co-treatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which associated with a loss of canonical Wnt signalling. This regenerative response was restored by agonist wash out or co-treatment 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 non-ligated state.