Genome-wide distribution of Pbx1/2/3 in mouse cortex at embryonic day 12.5 [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE78720 | GEO | 2016/02/27
SECONDARY ACCESSION(S): PRJNA313319
REPOSITORIES: GEO
Similar Datasets
Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. Chromatin immunoprecipitation was performed using antibody against Pbx1/2/3/ (sc-888, Santa Cruz). Wild type E12.5 mouse whole cortex was used for the analysis.
2016-02-27 | E-GEOD-78720 | biostudies-arrayexpress
Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate. Chromatin immunoprecipitation was performed using antibody against Pbx1/2/3 (sc-888, Santa Cruz). Wild type E15.5 mouse whole cortex was used for the analysis.
2016-03-12 | E-GEOD-79152 | biostudies-arrayexpress
Project description:We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/ sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate.
2016-03-12 | GSE79152 | GEO
Project description:Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons. Mouse E14.5 neocortices and Postnatal day (P) 0.5 brains: E14.5 neocortices KO, 3; E14.5 neocortices WT, 3; Postnatal day (P) 0.5 brains frontal WT, 4; Postnatal day (P) 0.5 brains frontal KO, 4; Postnatal day (P) 0.5 brains parietal WT, 4; Postnatal day (P) 0.5 brains parietal KO, 4; Postnatal day (P) 0.5 brains occipital WT, 4; Postnatal day (P) 0.5 brains occipital KO, 4.
2010-07-27 | E-GEOD-22371 | biostudies-arrayexpress
Project description:Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
2010-07-27 | GSE22371 | GEO
Project description:Two critical events that are required for normal transition from fetal to extrauterine life are development of the alveoli that allow for efficient gas exchange in the lung and relaxation of the pulmonary vascular smooth muscle. Patients with congenital diaphragmatic hernia (CDH) have abnormal lung and pulmonary vascular development that results in a lethal combination of lung hypoplasia and pulmonary hypertension. To better understand the mechanisms responsible for abnormal lung and pulmonary vascular development and function we generated Pbx1/2 conditional knockout mice that lack Pbx1 and Pbx2 expression in the lung mesenchyme. Pbx1 has previously been shown to be required for normal diaphragm development, however its role in alveologenesis, and the mechanisms responsible for pulmonary hypertension, has not been studied. We found that Pbx1/2 CKO mice have failure of alveologenesis and die of severe pulmonary hypertension by 2 to 3 weeks of age. In order to better understand the downstream genetic mis-regulation caused by deletion of Pbx1/2, and identify their potential transcriptional targets, we carried out transcriptional profiling of Pbx1/2 CKO and control mice starting at postnatal day 3 (P3), when a histological phenotype first becomes apparent, and then working back to the time of birth (P0), and embryonic day 14 (E14) when the pulmonary vascular smooth muscle is developing. In this dataset are the expression data obtained from dissected embryonic and early postnatal lungs of Pbx1/2 CKO and control mice. Pbx1/2 CKO mice are homozygous null for Pbx2 with conditional deletion of Pbx1 in the lung mesenchyme directed by Tbx4 Cre (Tbx4 Cre/wild-type; Pbx1 flox/flox; Pbx2 delta/delta). Control mice are homozygous null for Pbx2 and are heterozygous for Pbx1 in the lung mesenchyme (Tbx4 Cre/wild-type; Pbx1 flox/wild-type; Pbx2 delta/delta). These data are used to identify the transcriptional targets and down-stream effectors of PBX transciptional regulation in the lung.
2017-11-02 | GSE106399 | GEO
Project description:In vertebrates, body axis elongation is fuelled by bipotent neuromesodermal progenitors (NMPs), which support the development of both spinal cord and paraxial mesoderm (PM). HOX transcription factors have been historically implicated in axial elongation, with their sequential activation playing a fundamental role in timing PM development. PBX1 and PBX2 are obligate anterior HOX cofactors, and therefore they represent prominent candidates for controlling the distinct response to individual HOX factors. In our work, we have demonstrated that PBX proteins play a fundamental role in promoting the expression of PM genes, including the master regulator Mesogenin1 (Msgn1). To address the role of PBX proteins in PM differentiation, RNA-seq was performed on wild-type (WT) and Pbx1/Pbx2 double-knockout (Pbx1/2-DKO) EpiSCs differentiated in vitro to pre-somitic mesoderm (PSM) at different time-points (12 hours and 24 hours). To establish the direct transcriptional regulation of Msgn1 by PBX/HOX, we employed the CRISPR/Cas9 technology to generate lines carrying base-pair substitutions on the Msgn1 promoter (pMsgn1-mut) that abrogate the recruitment of PBX/HOX complexes, and we performed RNA-seq of pMsgn1-mut EpiSCs differentiated in vitro to PSM at 24 hours. All differentiation experiments were performed in biological triplicates with WT and Pbx1/2-DKO lines, and in biological duplicates with pMsgn1-mut lines.
2021-07-21 | E-MTAB-9773 | biostudies-arrayexpress
Project description:In vertebrates, body axis elongation is fuelled by bipotent neuromesodermal progenitors (NMPs), which support the development of both spinal cord and paraxial mesoderm (PM). WNT signalling sustains both NMP expansion and PM differentiation, but the mechanism by which it distinguishes between these alternative fates is unknown. HOX transcription factors have been historically implicated in axial elongation, with their sequential activation playing a fundamental role in timing PM development. PBX1 and PBX2 are obligate anterior HOX cofactors, and therefore they represent prominent candidates for controlling the distinct response to individual HOX factors. In our work, we have demonstrated that PBX proteins generate the DNA-binding context that allows recruitment of the WNT-effector LEF1, and consequently promote the expression of PM genes. Here, we wanted to identify the chromatin binding pattern of PBX1, PBX2 and LEF1 during the first 48 hours of pre-somitic mesoderm (PSM) in vitro differentiation, by performing chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) at different time-points (EpiSCs, 6 hours, 12 hours, 24 hours, 48 hours). To address the impact of PBX loss on LEF1 recruitment to chromatin, we additionally performed ChIP-seq in wild-type (WT) and Pbx1/Pbx2 double-knockout (Pbx1/2-DKO) EpiSCs differentiated in vitro to PSM at different time-points (EpiSCs, 12 hours, 24 hours, 48 hours).
2021-07-21 | E-MTAB-9775 | biostudies-arrayexpress
Project description:In vertebrates, body axis elongation is fuelled by bipotent neuromesodermal progenitors (NMPs), which support the development of both spinal cord and paraxial mesoderm (PM). WNT signalling sustains both NMP expansion and PM differentiation, but the mechanism by which it distinguishes between these alternative fates is unknown. HOX transcription factors have been historically implicated in axial elongation, with their sequential activation playing a fundamental role in timing PM development. PBX1 and PBX2 are obligate anterior HOX cofactors, and therefore they represent prominent candidates for controlling the distinct response to individual HOX factors. In our work, we have demonstrated that PBX/HOX complexes establish a permissive chromatin landscape for de novo recruitment of the WNT-effector LEF1 on PM genes, including the master regulator Mesogenin1 (Msgn1). To assess the PBX-dependent changes in chromatin accessibility during PM differentiation, we performed ATAC-seq of wild-type (WT) and Pbx1/Pbx2 double-knockout (Pbx1/2-DKO) EpiSCs differentiated in vitro to pre-somitic mesoderm (PSM) at different time-points (EpiSCs, 6 hours, 12 hours, 24 hours, 36 hours, 48 hours). To assess the direct consequence of PBX/HOX binding on chromatin accessibility, we employed the CRISPR/Cas9 technology to generate lines carrying base-pair substitutions on the Msgn1 promoter (pMsgn1-mut) that abrogate the recruitment of PBX/HOX complexes, and we performed ATAC-seq of pMsgn1-mut EpiSCs differentiated in vitro to PSM at different time-points (12 hours, 24 hours, 36 hours, 48 hours).
2021-07-21 | E-MTAB-9776 | biostudies-arrayexpress
Project description:In vertebrates, body axis elongation is fuelled by bipotent neuromesodermal progenitors (NMPs), which support the development of both spinal cord and paraxial mesoderm (PM). NMPs reside in the caudal lateral epiblast and tailbud, from where they sustain axial elongation. HOX transcription factors have been historically implicated in axial elongation, with their sequential activation playing a fundamental role in timing PM development. PBX1 and PBX2 are obligate anterior HOX cofactors, and therefore they represent prominent candidates for controlling the distinct response to individual HOX factors. To pinpoint the role of PBX proteins in the development of pre-somitic mesoderm, single-cell RNA sequencing (scRNA-seq) was performed on cells isolated from the tailbuds of control, Pbx1/Pbx2 compound (Pbx1/2-com) and Pbx1/Pbx2 double-mutant (Pbx1/2-DKO) embryos at embryonic days 8.5 and 9.0. Single cells from at least three embryos per genotype and stage were FACS-sorted into 384-well capture plates, and scRNA-seq was performed using MARS-seq (Jaitin D.A. et al., Science, 343, 776-779 (2014)). As a spike-in internal control for batch-effect correction, 71 EpiSCs cultivated in vitro were sorted into each plate, together with 311 cells from embryonic tailbuds. Two wells were left empty in each plate, as a no-cell control during data analysis.
2021-07-21 | E-MTAB-9785 | biostudies-arrayexpress