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Molecular and Cellular Biology, September 2000, p. 6579-6586, Vol. 20, No. 17
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Retinoic Acid Regulation of Cdx1: an Indirect Mechanism for Retinoids and Vertebral Specification

Martin Houle,1,2 Panagiotis Prinos,2 Angelo Iulianella,1,2 Nathalie Bouchard,2 and David Lohnes1,2,3,*

Department of Molecular Biology, Université de Montréal,1 Division of Experimental Medicine, McGill University,3 and Institut de Recherches Cliniques de Montréal,2 Montréal, Québec, Canada H2W 1R7

Received 19 April 2000/Accepted 25 May 2000

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.

* Corresponding author. Mailing address: Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins, ouest, Montréal, Québec, Canada H2W 1R7. Phone: (514) 987-5668. Fax: (514) 987-5767. E-mail: lohnesd{at}ircm.qc.ca.

Molecular and Cellular Biology, September 2000, p. 6579-6586, Vol. 20, No. 17
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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