Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos -13 somites embryonic stage
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE17660 | GEO | 2009/10/19
SECONDARY ACCESSION(S): PRJNA123383
REPOSITORIES: GEO
Similar Datasets
Project description:Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal uro-rectal structures. We show that trunk Hox genes stimulate axial extension as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem to differentially orchestrate posterior expansion of embryonic tissues during axial morphogenesis as an integral part of their function in specifying head-to-tail identity. In addition, we present evidence that Cdx and Hox transcription factors exert these effects by controlling Wnt signaling. Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling in the posterior growth zone, may likewise play a role in timing the trunk-tail transition.
2009-10-19 | GSE17658 | GEO
Project description:Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal uro-rectal structures. We show that trunk Hox genes stimulate axial extension as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem to differentially orchestrate posterior expansion of embryonic tissues during axial morphogenesis as an integral part of their function in specifying head-to-tail identity. In addition, we present evidence that Cdx and Hox transcription factors exert these effects by controlling Wnt signaling. Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling in the posterior growth zone, may likewise play a role in timing the trunk-tail transition. Experiment Overall Design: A micro-array screen of down regulated and upregulated genes in Cdx2+/-Cdx4-/- mutant embryos versus wildtype embryos was performed at the embryonic stage of 13 somites. RNA was isolated from the posterior part of the embryos dissected at the same axial level using the last somite boundary as a landmark. Posterior tissues from pools of 7 embryos of each genotype were pooled. The labeled cRNAs were hybridized on 4X44K Agilent Whole Mouse Genome dual colour Microarrays (G4122F) in a dye swap experiment, resulting in two individual microarrays.
2009-10-23 | E-GEOD-17660 | biostudies-arrayexpress
Project description:Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal uro-rectal structures. We show that trunk Hox genes stimulate axial extension as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem to differentially orchestrate posterior expansion of embryonic tissues during axial morphogenesis as an integral part of their function in specifying head-to-tail identity. In addition, we present evidence that Cdx and Hox transcription factors exert these effects by controlling Wnt signaling. Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling in the posterior growth zone, may likewise play a role in timing the trunk-tail transition. Experiment Overall Design: A micro-array screen of down regulated and upregulated genes in Cdx2+/-Cdx4-/- mutant embryos versus wildtype embryos was performed at the embryonic stage of 5/6 somites. RNA was isolated from the posterior part of the embryos dissected at the same axial level using the last somite boundary as a landmark. Posterior tissues from pools of 10 embryos of each genotype were pooled. The labeled cRNAs were hybridized on 4X44K Agilent Whole Mouse Genome dual colour Microarrays (G4122F) in two dye swap experiments, resulting in four individual microarrays.
2009-10-23 | E-GEOD-17658 | biostudies-arrayexpress
Project description: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 urorectal 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 signalling during the laying down of urorectal 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 sometimes leading to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signalling, 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. We used dissected Cdx2 null mutant versus wild type embryos at the 4/5 somite and 7/8 somite stage. RNA was isolated from the posterior part of the embryos (20 embryos of each genotype and stage), dissected at the same axial levels by using the last somite boundary and the base of the allantois as landmarks. Differentially labelled cRNA from the Cdx2 and control embryos were hybridized on 4X44K Agilent Whole Mouse Genome dual colour Microarrays (G4122F) in two dye swap experiments and two technical replicates, resulting in eight individual arrays.
2011-12-01 | E-GEOD-30113 | biostudies-arrayexpress
Project description:In vertebrate embryos, anterior tissues are generated early, followed by the other axial structures that emerge sequentially from a posterior growth zone. The genetic network driving posterior axial elongation in mice, and its disturbance in mutants with posterior truncation are not yet fully understood. We show that the combined expression of Cdx2 and T Brachyury is essential to establish the core signature of posterior axial progenitors. Cdx2 and T Brachyury are required for extension of a similar trunk portion of the axis. Simultaneous loss of function of these two genes disrupts axial elongation to a much greater extent than each single mutation alone. We identify and validate common targets for Cdx2 and T Brachyury in vivo including Wnt and Fgf pathway components active in the axial progenitor niche. Our data demonstrate that integration of the Cdx/Hox and T Brachyury transcriptional networks controls differential axial growth during vertebrate trunk elongation.
2016-12-20 | GSE84899 | GEO
Project description: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 urorectal 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 signalling during the laying down of urorectal 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 sometimes leading to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signalling, 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.
2011-12-01 | GSE30113 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE17658: Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos - 5/6 somites embryonic stage; GSE17660: Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos -13 somites embryonic stage Experiment Overall Design: Refer to individual Series
2009-10-23 | E-GEOD-17663 | biostudies-arrayexpress
Project description:The vertebrate main-body axis is laid down during embryonic stages in an anterior-to-posterior (head-to-tail) direction, driven and supplied by posteriorly located progenitors. For the vertebral column, the process of axial progenitor cell expansion that drives axis elongation, and the process of segmentation which allocates these progenitors into repeating vertebral units, occurs seemingly uninterrupted from the first to the last vertebra. Nonetheless, there is clear developmental and evolutionary support for two discrete modules controlling processes within different axial regions: a trunk module and a tail module. The secreted signal Gdf11 has been identified as a principal regulator of timing the trunk-to-tail (T-to-T) transition, but has pleiotropic effects across much of the main body axis, highlighting the need to reveal intrinsic regulatory networks that function to exclusively control one or the other module. Here, we identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of elongation, patterning and lineage allocation specifically within the trunk region of the mouse. Both gain- and loss-of-function in vivo analysis revealed that the precise level of Nr6a1 acts as a rheostat, expanding or contracting vertebral number of the trunk region autonomously from other axial regions. Moreover, the timely clearance of Nr6a1 observed at the T-to-T transition was essential in allowing the tail module to operate correctly. In parallel with these effects on vertebral number, we show that Nr6a1 controls the timely progression of global Hox signatures within axial progenitors, preventing the precocious expression of multiple posterior Hox genes as the trunk is being laid down and thus reinforcing that patterning and elongation are coordinated. Finally, our data supports a crucial role for Nr6a1 in regulating gene regulatory networks that guide cell lineage choice of axial progenitors between neural and mesodermal fate. Collectively, our data reveals an axially-restricted role for Nr6a1 in all major cellular and tissue-level events required for vertebral column formation, supporting the view that modulation of Nr6a1 expression level or function may underpin evolutionary changes in axial formulae that exclusively alter the trunk region.
2023-01-03 | GSE180426 | GEO
Project description:The vertebrate main-body axis is laid down during embryonic stages in an anterior-to-posterior (head-to-tail) direction, driven and supplied by posteriorly located progenitors. For the vertebral column, the process of axial progenitor cell expansion that drives axis elongation, and the process of segmentation which allocates these progenitors into repeating vertebral units, occurs seemingly uninterrupted from the first to the last vertebra. Nonetheless, there is clear developmental and evolutionary support for two discrete modules controlling processes within different axial regions: a trunk module and a tail module. The secreted signal Gdf11 has been identified as a principal regulator of timing the trunk-to-tail (T-to-T) transition, but has pleiotropic effects across much of the main body axis, highlighting the need to reveal intrinsic regulatory networks that function to exclusively control one or the other module. Here, we identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of elongation, patterning and lineage allocation specifically within the trunk region of the mouse. Both gain- and loss-of-function in vivo analysis revealed that the precise level of Nr6a1 acts as a rheostat, expanding or contracting vertebral number of the trunk region autonomously from other axial regions. Moreover, the timely clearance of Nr6a1 observed at the T-to-T transition was essential in allowing the tail module to operate correctly. In parallel with these effects on vertebral number, we show that Nr6a1 controls the timely progression of global Hox signatures within axial progenitors, preventing the precocious expression of multiple posterior Hox genes as the trunk is being laid down and thus reinforcing that patterning and elongation are coordinated. Finally, our data supports a crucial role for Nr6a1 in regulating gene regulatory networks that guide cell lineage choice of axial progenitors between neural and mesodermal fate. Collectively, our data reveals an axially-restricted role for Nr6a1 in all major cellular and tissue-level events required for vertebral column formation, supporting the view that modulation of Nr6a1 expression level or function may underpin evolutionary changes in axial formulae that exclusively alter the trunk region.
2023-01-03 | GSE179858 | GEO