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Publication
Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone
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| artigo principal | 5.46 MB | Adobe PDF | ||
| material suplementar 1 | 68.57 KB | Adobe PDF | ||
| material suplementar 2 | 47.71 KB | Adobe PDF | ||
| material suplementar 3 | 94.46 KB | Adobe PDF | ||
| material suplementar 4 | 99.2 KB | Adobe PDF |
Advisor(s)
Abstract(s)
Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects, including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele in the Cdx4-null background (Cdx2/4), transgenic embryos precociously expressing Hox13 genes and a novel Wnt3a hypomorph mutant all manifest a comparable phenotype with similar uro-rectal defects. Phenotype and transcriptome analysis in early Cdx mutants, genetic rescue experiments and gene expression studies lead us to propose that Cdx transcription factors act via Wnt signaling during the laying down of uro-rectal mesoderm, and that they are operative in an early phase of these events, at the site of tissue progenitors in the posterior growth zone of the embryo. Cdx and Wnt mutations and premature Hox13 expression also cause similar neural dysmorphology, including ectopic neural structures that sometimes lead to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signaling and the temporal control of posterior Hox gene expression in posterior morphogenesis in the different embryonic germ layers. They shed a new light on the etiology of the caudal dysplasia or caudal regression range of human congenital defects.
Description
Keywords
Animals Cell Shape Embryo, Mammalian Female Hedgehog Proteins Homeodomain Proteins Male Mice Mice, Inbred C57BL Mice, Transgenic Neural Tube Transcription Factors Tretinoin Wnt Proteins Wnt3 Protein Wnt3A Protein Gene Expression Regulation, Developmental Signal Transduction
Citation
Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone Cesca van de Ven, Monika Bialecka, Roel Neijts, Teddy Young, Jennifer E. Rowland, Emma J. Stringer, Carina Van Rooijen, Frits Meijlink, Ana Nóvoa, Jean-Noel Freund, Moises Mallo, Felix Beck, Jacqueline Deschamps Development 2011 138: 3451-3462; doi: 10.1242/dev.066118
Publisher
Company of Biologists