title: 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.
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.
authors.affiliation: 1 Life and Health Sciences, Aston University , Birmingham, United Kingdom .
authors.forename: Htoo Aung
authors.initials: HA
authors.lastname: Wai
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Hironori
authors.initials: H
authors.lastname: Wada
authors.forename: Ferenc
authors.initials: F
authors.lastname: Müller
authors.forename: Ann Beatrice
authors.initials: AB
authors.lastname: Vernallis
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Brown
authors.forename: William Eustace Basil
authors.initials: WE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D055495:Neurogenesis; D010012:Osteogenesis; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D019170:Somites / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish; D000097768:Retinoic Acid Receptor gamma
chemical_list: D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D055758:SOX9 Transcription Factor; D020825:T-Box Domain Proteins; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C103172:T-box transcription factor 5