Retinoic acid regulation of Cdx1: an indirect mechanism for retinoids and vertebral specification.
Retinoic acid (RA) is required for diverse developmental programs, including vertebral specification. Both RA receptor disruption and excess RA result in homeotic transformations of the axial skeleton. These effects are believed to occur through altered expression of Hox genes, several of which have been demonstrated to be direct RA targets. Members of the cdx (caudal) homeobox gene family are also implicated in regulating Hox expression. Disruption of cdx1 results in vertebral homeotic transformations and alteration of Hox expression boundaries; similar homeosis is also observed in cdx2 heterozygotes. In Xenopus, gain or loss of Cdx function affects vertebral morphogenesis through a mechanism that also correlates with altered Hox expression. Taken together with the finding of putative Cdx binding motifs in several Hox promoters, these data strongly support a role for Cdx members in direct regulation of expression of at least some Hox genes. Most retinoid-responsive Hox genes have not been demonstrated to be direct RA targets, suggesting that intermediaries are involved. Based on these findings, we hypothesized that one or more cdx members may transduce the effects of RA on Hox transcription. Consistent with this, we present evidence that cdx1 is a direct RA target gene, suggesting an additional pathway for retinoid-dependent vertebral specification.
Department of Molecular Biology, Université de Montréal, Montréal, Québec, Canada H2W 1R7.
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Houle
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Prinos
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Iulianella
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Bouchard
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Lohnes
D000818:Animals; D030161:Avian Proteins; D015152:Blotting, Northern; D000071616:CDX2 Transcription Factor; D002478:Cells, Cultured; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D029867:Xenopus Proteins
D030161:Avian Proteins; D000071616:CDX2 Transcription Factor; C491272:Cdx1 protein, mouse; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D029867:Xenopus Proteins; C000605378:cdx2 protein, Xenopus; D014212:Tretinoin