Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone

C. van de Ven, M. Bialecka, R. Neijts, T. Young, J.E. Rowland, E.J. Stringer, C.R. van Rooijen, F. Meijlink, A. Novoa, J.N. Freund, M. Mallo, F. Beck, J. Deschamps

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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. [KEYWORDS: Animals, Cell Shape, Embryo, Mammalian/ metabolism, Female, Gene Expression Regulation, Developmental, Hedgehog Proteins/metabolism, Homeodomain Proteins/genetics/ metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neural Tube/cytology/ metabolism, Signal Transduction, Transcription Factors/genetics/ metabolism, Tretinoin/metabolism, Wnt Proteins/genetics/ metabolism, Wnt3 Protein, Wnt3A Protein]
Original languageEnglish
Pages (from-to)3451-3462
JournalDevelopment
Volume138
Issue number16
DOIs
Publication statusPublished - 2011

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