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XB-ART-48992
Development June 1, 2014; 141 (11): 2260-70.

Active repression by RARγ signaling is required for vertebrate axial elongation.

Janesick A , Nguyen TT , Aisaki K , Igarashi K , Kitajima S , Chandraratna RA , Kanno J , Blumberg B .


Abstract
Retinoic acid receptor gamma 2 (RARγ2) is the major RAR isoform expressed throughout the caudal axial progenitor domain in vertebrates. During a microarray screen to identify RAR targets, we identified a subset of genes that pattern caudal structures or promote axial elongation and are upregulated by increased RAR-mediated repression. Previous studies have suggested that RAR is present in the caudal domain, but is quiescent until its activation in late stage embryos terminates axial elongation. By contrast, we show here that RARγ2 is engaged in all stages of axial elongation, not solely as a terminator of axial growth. In the absence of RA, RARγ2 represses transcriptional activity in vivo and maintains the pool of caudal progenitor cells and presomitic mesoderm. In the presence of RA, RARγ2 serves as an activator, facilitating somite differentiation. Treatment with an RARγ-selective inverse agonist (NRX205099) or overexpression of dominant-negative RARγ increases the expression of posterior Hox genes and that of marker genes for presomitic mesoderm and the chordoneural hinge. Conversely, when RAR-mediated repression is reduced by overexpressing a dominant-negative co-repressor (c-SMRT), a constitutively active RAR (VP16-RARγ2), or by treatment with an RARγ-selective agonist (NRX204647), expression of caudal genes is diminished and extension of the body axis is prematurely terminated. Hence, gene repression mediated by the unliganded RARγ2-co-repressor complex constitutes a novel mechanism to regulate and facilitate the correct expression levels and spatial restriction of key genes that maintain the caudal progenitor pool during axial elongation in Xenopus embryos.

PubMed ID: 24821986
Article link: Development

Genes referenced: cyp26a1 esr-5 gdf3 hes5.3 hes5.7 hoxa11 hoxa9 hoxc10 hoxc11 hoxc13 hoxd10 hoxd9 mespa msgn1 myod1 ncor2 not pnp rab40b rarg ripply2.1 ripply2.2 tbx6 tbxt.2

GEO Series:
   GSE57352: NCBI


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