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ID: 16910.0, MPI für biophysikalische Chemie / Molekulare Zellbiologie (Prof. Peter Gruss)
RAR gamma and Cdx1 interactions in vertebral patterning
Authors:Allan, D.; Houle, M.; Bouchard, N.; Meyer, B.; Gruss, P.; Lohnes, D.
Date of Publication (YYYY-MM-DD):2001-12-01
Title of Journal:Developmental Biology
Issue / Number:1
Start Page:46
End Page:60
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Exogenous retinoic acid (RA) can evoke vertebral homeosis when administered during late gastrulation. These vertebral transformations correlate with alterations of the rostral limit of Hox gene expression in the prevertebrae, suggesting that retinoid signaling regulates the combinatorial expression of Hox genes dictating vertebral identity. Conversely, loss of certain RA receptors (RARs) results in anterior homeotic transformations principally affecting the cervical region. Despite these observations, the relationship between retinoid signaling, somitic Hox expression, and vertebral patterning is poorly understood. The members of the murine Cdx family (Cdx1, Cdx2, and Cdx4) are the homologues of Drosophila caudal and encode homeobox-containing transcription factors. Cdx1 homozygous null mutants exhibit anterior homeotic transformations, some of which are reminiscent of those in RAR gamma null offspring. in Cdx1 mutants, these transformations occur concomitant with posteriorized prevertebral expression of certain Hox genes. Cdx1 has recently been demonstrated to be a direct RA target, suggesting an indirect means by which retinoid signaling may impact vertebral patterning. To further investigate this relationship, a complete allelic series of Cdx1-RAR gamma mutants was generated and the skeletal phenotype assessed either following normal gestation or after administration of RA. Synergistic interactions between these null alleles were observed in compound mutants, and the full effects of exogenous RA on vertebral morphogenesis required Cdx1. These findings are consistent with a role for RA upstream of Cdx1 as regards axial patterning. However, exogenous RA attenuated several defects inherent to Cdx1 null mutants. This finding, together with the increased phenotypic severity of RAR gamma -Cdx1 double null mutants relative to single nulls, suggests that these pathways also function in parallel, likely by converging on common targets. (C) 2001 Academic Press.
Free Keywords:retinoic acid receptor; Cdx1; vertebral patterning; somite; Hox; RARE
Comment of the Author/Creator:Date: 2001, DEC 1
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Peter Gruss / 160
External Affiliations:McGill Univ, Div Expt Med, 110 Ave des Pins Ouest, Montreal, PQ; H2W 1R7, Canada; McGill Univ, Div Expt Med, Montreal, PQ H2W 1R7, Canada; Univ Montreal, Dept Mol Biol, Montreal, PQ H2W 1R7, Canada; Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada
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