Affiliation:
1. Institut de Recherches Cliniques de Montréal
2. Department of Molecular Biology, Université de Montréal
3. Department of Experimental Medicine, McGill University, Montréal, Québec, Canada
Abstract
ABSTRACT
The
Cdx1
gene product is essential for normal anterior-posterior vertebral patterning. Expression of
Cdx1
is regulated by several pathways implicated in anterior-posterior patterning events, including retinoid and Wnt signaling. We have previously shown that retinoic acid plays a key role in early stages of
Cdx1
expression at embryonic day 7.5 (E7.5), while both Wnt3a signaling and an autoregulatory loop, dependent on Cdx1 itself, are involved in later stages of expression (E8.5 to E9.5). This autoregulation is reflected by the ability of Cdx1 to affect expression from proximal
Cdx1
promoter sequences in tissue culture. However, this region is devoid of a demonstrable Cdx response element(s). We have now found that Cdx1 and LEF1, a nuclear effector of Wnt signaling, synergize to induce expression from the
Cdx1
promoter through previously documented LEF/T-cell factor response elements. We also found a direct physical interaction between the homeodomain of Cdx1 and the B box of LEF1, suggesting a basis for this synergy. Consistent with these observations, analysis of
Cdx1 Wnt3a
vt
compound mutants demonstrated that Wnt and Cdx1 converged on
Cdx1
expression and vertebral patterning in vivo. Further data suggest that Cdx-high-mobility group box interactions might be involved in a number of additional pathways.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
68 articles.
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