Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone
| Autor: | Felix Beck, Jacqueline Deschamps, Frits Meijlink, Roel Neijts, Jennifer E. Rowland, Teddy Young, Moisés Mallo, Ana Nóvoa, Jean-Noël Freund, Monika Bialecka, Carina van Rooijen, Emma J. Stringer, Cesca van de Ven |
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| Přispěvatelé: | Hubrecht Institute [Utrecht, Netherlands], University Medical Center [Utrecht]-Royal Netherlands Academy of Arts and Sciences (KNAW), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, University of Leicester, De l'homéostasie tissulaire au cancer et à l'inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM), univOAK, Archive ouverte, Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Mesoderm Neural Tube Morphogenesis Mice Transgenic Tretinoin [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Wnt3 Protein 03 medical and health sciences Mice 0302 clinical medicine Wnt3A Protein medicine Animals CDX2 Transcription Factor Hedgehog Proteins CDX2 Hox gene Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology Cell Shape 030304 developmental biology Genetics Homeodomain Proteins 0303 health sciences 030302 biochemistry & molecular biology Neural tube Wnt signaling pathway Gene Expression Regulation Developmental Embryo Mammalian Phenotype Cell biology Mice Inbred C57BL Wnt Proteins medicine.anatomical_structure embryonic structures Female 030217 neurology & neurosurgery Developmental Biology Transcription Factors Signal Transduction |
| Zdroj: | Development (Cambridge, England) Development (Cambridge, England), Company of Biologists, 2011, 138 (16), pp.3451-3462. ⟨10.1242/dev.066118⟩ Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Development, 138(16), 3451-3462. Company of Biologists Ltd |
| ISSN: | 0950-1991 1477-9129 |
| DOI: | 10.1242/dev.066118⟩ |
| Popis: | 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] |
| Databáze: | OpenAIRE |
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