Similar Datasets
Project description:The trunk axial skeleton develops from paraxial mesoderm cells. Our recent study demonstrated that conditional knockout of the stem cell factor Sall4 in mice by TCre caused tail truncation and a disorganized axial skeleton posterior to the lumbar level. Based on this phenotype, we hypothesized that, in addition to the previously reported role of Sall4 in neuromesodermal progenitors, Sall4 is involved in the development of the paraxial mesoderm tissue. ATAC-seq in TCre; Sall4 mutant posterior trunk mesoderm shows that Sall4 knockout reduces chromatin accessibility. We found that Sall4- dependent open chromatin status drives activation and repression of WNT signaling activators and repressors, respectively, to promote WNT signaling. Moreover, footprinting analysis of ATAC-seq data suggests that Sall4-dependent chromatin accessibility facilitates CTCF binding, which contributes to the repression of neural genes within the mesoderm. This study unveils multiple mechanisms by which Sall4 regulates paraxial mesoderm development by directing activation of mesodermal genes and repression of neural genes.
2024-02-13 | GSE217671 | GEO
Project description:During mammalian embryogenesis, axial elongation of the neural tube is critical for establishing the anterior-posterior body axis, but is difficult to interrogate directly because it occurs post-implantation. Here we report an organoid model of neural tube extension using human pluripotent stem cell (hPSC) aggregates that recapitulates the morphologic and temporal gene expression patterns of neural tube development. Axially extending organoids consisted of longitudinally elongated epithelial compartments and contained TBXT(+)SOX2(+) neuromesodermal progenitors, PAX6(+) Nestin(+) neural progenitor populations, and MEOX1(+) paraxial mesoderm populations. Wnt agonism stimulated axial extensions in a dose-dependent manner and elongated organoids displayed regionalized rostral-caudal HOX gene expression, with hindbrain (HOXB1) expression distinct from brachial (HOXC6) and thoracic (HOXB9) expression. CRISPR interference-mediated silencing of BMP inhibitors induced elongation phenotypes that mimicked murine knockout models, and knock-down of the downstream Wnt target, TBXT, increased neuroepithelial compartmentalization and resulted in multiple extensions. These results indicate the potent morphogenic capacity of hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.
2021-05-28 | GSE155383 | GEO
Project description:During mammalian embryogenesis, axial elongation of the neural tube is critical for establishing the anterior-posterior body axis, but is difficult to interrogate directly because it occurs post-implantation. Here we report an organoid model of neural tube extension using human pluripotent stem cell (hPSC) aggregates that recapitulates the morphologic and temporal gene expression patterns of neural tube development. Axially extending organoids consisted of longitudinally elongated epithelial compartments and contained TBXT(+)SOX2(+) neuromesodermal progenitors, PAX6(+) Nestin(+) neural progenitor populations, and MEOX1(+) paraxial mesoderm populations. Wnt agonism stimulated axial extensions in a dose-dependent manner and elongated organoids displayed regionalized rostral-caudal HOX gene expression, with hindbrain (HOXB1) expression distinct from brachial (HOXC6) and thoracic (HOXB9) expression. CRISPR interference-mediated silencing of BMP inhibitors induced elongation phenotypes that mimicked murine knockout models, and knock-down of the downstream Wnt target, TBXT, increased neuroepithelial compartmentalization and resulted in multiple extensions. These results indicate the potent morphogenic capacity of hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.
2021-05-28 | GSE155382 | GEO
Project description:Differentiation analysis of Mouse Posterior Neural tube
| PRJNA436907 | ENA
Project description:Background: Spina bifida is one of the most common and life threatening human congenital defects. Despite considerable effort and investigations, the causes and mechanisms underlying this malformation remain poorly characterized. In order to better understand pathogenesis of this abnormality, we conducted a microarray study to compare gene expression profiles between two mouse models, CLX-Splotch and Fkbp8Gt(neo), that both have spina bifida. Results: To compare the gene expression profiles in these two mouse models we performed microarray analysis using Mouse Whole Genome CodeLink Bioarray. We compared the level of gene expression between wildtype and homozygous mutant embryos in Fkbp8Gt(neo) and CXL-Splotch separately. A total of 54 genes were determined to be differentially expressed (25 down, 29 up) in the posterior neural tube of Fkbp8Gt(neo) mice embryos; while 73 genes were differentially expressed (56 down, 17 up) in the CXL-Splotch mouse. The only two genes that showed decreased expression in both mutants were v-ski sarcoma viral oncogene homolog (Ski) and Zic1, a transcription factor member of the zinc finger family. Interestingly, when Gene Ontology (GO) analysis was performed on all of the differentially expressed genes, there was a striking enrichment of genes associated with mesoderm development and central nervous system development in CLX-Splotch, whereas in Fkbp8Gt(neo) genes involved in dorsal/ventral pattern formation, cell fate specification, and positive regulation of cell differentiation were distinguished. This SuperSeries is composed of the following subset Series: GSE25974: Gene expression-based analysis of neural tube closure for the posterior neuropore of Fkbp8 embryos at E9.5 GSE25975: Gene expression-based analysis of neural tube closure for the posterior neuropore of Splotch embryos at E9.5
2010-12-10 | E-GEOD-25983 | biostudies-arrayexpress
Project description:Three wildtype and three nullizygous embryonic posterior neural tube tissues were collected at embryonic day 9.5 and the gene expression patterns were profiled on CodeLink Mouse Whole Genome Bioarrays.
2010-12-10 | GSE25975 | GEO
Project description:Three wildtype and three nullizygous embryonic posterior neural tube tissues were collected at embryonic day 9.5 and the gene expression patterns were profiled on CodeLink Mouse Whole Genome Bioarrays.
2010-12-10 | GSE25974 | 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. 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: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:To better understand the role of Geminin during germ layer specification, we bred floxed Geminin mice to Mox2-Cre mice. Mutants (fl/fl; cre/o) had spinal neural tube defects with complete penetrance. We obtained neural tube and paraxial tissue by laser capture microdissection and analyzed total RNA by microarray. Spinal neural tube and paraxial tissue were obtained separately by laser capture microdissection from wild-type and mutant E10.5 embryos. There were 2 replicates of each sample.
2014-09-30 | E-GEOD-42052 | biostudies-arrayexpress