Cdx2 regulation of posterior development through non-Hox targets.
The homeodomain transcription factors Cdx1, Cdx2 and Cdx4 play essential roles in anteroposterior vertebral patterning through regulation of Hox gene expression. Cdx2 is also expressed in the trophectoderm commencing at E3.5 and plays an essential role in implantation, thus precluding assessment of the cognate-null phenotype at later stages. Cdx2 homozygous null embryos generated by tetraploid aggregation exhibit an axial truncation indicative of a role for Cdx2 in elaborating the posterior embryo through unknown mechanisms. To better understand such roles, we developed a conditional Cdx2 floxed allele in mice and effected temporal inactivation at post-implantation stages using a tamoxifen-inducible Cre. This approach yielded embryos that were devoid of detectable Cdx2 protein and exhibited the axial truncation phenotype predicted from previous studies. This phenotype was associated with attenuated expression of genes encoding several key players in axial elongation, including Fgf8, T, Wnt3a and Cyp26a1, and we present data suggesting that T, Wnt3a and Cyp26a1 are direct Cdx2 targets. We propose a model wherein Cdx2 functions as an integrator of caudalizing information by coordinating axial elongation and somite patterning through Hox-independent and -dependent pathways, respectively.
Savory
Joanne G A
JG
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
Bouchard
Nathalie
N
Pierre
Vicki
V
Rijli
Filippo M
FM
De Repentigny
Yves
Y
Kothary
Rashmi
R
Lohnes
David
D
D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D051379:Mice; D009154:Mutation; D000072516:Retinoic Acid 4-Hydroxylase; D015398:Signal Transduction / Q000235:genetics; D013131:Spine / Q000196:embryology; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; C496457:Fgf8 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D013629:Tamoxifen; D051524:Fibroblast Growth Factor 8; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase