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Molecular and Cellular Biology, September 2000, p. 6579-6586, Vol. 20, No. 17
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.
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
*
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.
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