TY - JOUR
T1 - 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
T2 - evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid
AU - Wai, Htoo Aung
AU - Kawakami, Koichi
AU - Wada, Hironori
AU - Müller, Ferenc
AU - Vernallis, Ann Beatrice
AU - Johnson, William Eustace Basil
AU - Brown, Geoffrey
PY - 2015/2/13
Y1 - 2015/2/13
N2 - 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.
AB - 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.
KW - Animals
KW - Embryonic Stem Cells
KW - Homeodomain Proteins
KW - Neural Crest
KW - Neurogenesis
KW - Osteogenesis
KW - Receptors, Retinoic Acid
KW - SOX9 Transcription Factor
KW - Somites
KW - T-Box Domain Proteins
KW - Tretinoin
KW - Wnt Signaling Pathway
KW - Zebrafish
U2 - 10.1089/scd.2014.0235
DO - 10.1089/scd.2014.0235
M3 - Article
C2 - 25233141
SN - 1547-3287
VL - 24
SP - 507
EP - 519
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 4
ER -