Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA117355 | ENA |
REPOSITORIES: ENA
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Project description:In the developing cerebral cortex different types of neurons and glial cells are born through a precisely controlled sequence of events. The fate of cortical progenitors, in turn, is determined by an elusive conundrum of temporally and spatially regulated signalling mechanisms. We found the DNA-binding transcription factor Sip1 (also known as Zfhx1b) to be produced at high levels in postmitotic neurons of the cerebral cortex. Conditional deletion of Sip1 in young neocortical neurons was found to induce premature and increased production of upper layer neurons at the expense of deep layer neurons. Furthermore, it caused precocious and increased generation of glial precursors during late corticogenesis, leading subsequently to enhanced astrocytogenesis at early postnatal stages. Expression profiling analysis indicated that the temporal shift in upper layer production coincides with overexpression of the neurotrophin-3 (NT3) gene and altered growth factor signalling in progenitors, while the premature gliogenesis is preceded by upregulation of fibroblast growth factor-9 (Fgf9) gene expression. Chromatin immunoprecipitation and in situ hybridization validates NT3 as a direct target of Sip1 in the cortex and confines the transcriptional repression by Sip1 to postmitotic neurons. Moreover, we show that exogenous application of Fgf9 in solution or via coated beads to wild-type cortical slices induces premature and excessive generation of glial precursors in the germinal zone. In conclusion, our data suggest that throughout corticogenesis Sip1 acts to restrain the level of production of secreted signalling factors in postmitotic neurons. These factors feed back to progenitor cells in order to regulate the timing of cell fate switch and the numbers of neurons and glial cells produced in the developing cerebral cortex.
2009-10-30 | GSE16699 | GEO
Project description:Schilling2009 - ERK distributive
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2009-04-20 18:57:44. The PottersWheel Model Definition file
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This model is described in the article:
Theoretical and experimental
analysis links isoform-specific ERK signalling to cell fate
decisions.
Schilling M, Maiwald T, Hengl S,
Winter D, Kreutz C, Kolch W, Lehmann WD, Timmer J,
Klingmüller U.
Mol. Syst. Biol. 2009; 5: 334
Abstract:
Cell fate decisions are regulated by the coordinated
activation of signalling pathways such as the extracellular
signal-regulated kinase (ERK) cascade, but contributions of
individual kinase isoforms are mostly unknown. By combining
quantitative data from erythropoietin-induced pathway
activation in primary erythroid progenitor (colony-forming unit
erythroid stage, CFU-E) cells with mathematical modelling, we
predicted and experimentally confirmed a distributive ERK
phosphorylation mechanism in CFU-E cells. Model analysis showed
bow-tie-shaped signal processing and inherently transient
signalling for cytokine-induced ERK signalling. Sensitivity
analysis predicted that, through a feedback-mediated process,
increasing one ERK isoform reduces activation of the other
isoform, which was verified by protein over-expression. We
calculated ERK activation for biochemically not addressable but
physiologically relevant ligand concentrations showing that
double-phosphorylated ERK1 attenuates proliferation beyond a
certain activation level, whereas activated ERK2 enhances
proliferation with saturation kinetics. Thus, we provide a
quantitative link between earlier unobservable signalling
dynamics and cell fate decisions.
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2010-10-27 | BIOMD0000000270 | BioModels
Project description:Wnt/b-catenin signaling regulates sequential fate decisions of murine cortical precursor cells
| PRJNA287701 | ENA
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:Necdin, a pleiotropic protein expressed predominantly in postmitotic neurons of mammals, regulates neuronal development and survival by interacting with various regulatory proteins. To understand a novel function of necdin, we analyzed gene expression profile of primary cortical neurons prepared from necdin-null mice at embryonic day 14.5. Wild-type and necdin-null cortical cells were prepared from mice at embryonic day 14.5. These cells were incubated in Neurobasal medium supplemented with B27 and differentiated into neurons for 4 days (>97% MAP2-positive postmitotic neurons). Three mice per genotype were used for analysis.
2016-03-10 | E-GEOD-63498 | biostudies-arrayexpress
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2022-10-11 | GSE212440 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2022-10-11 | GSE212439 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2023-04-28 | GSE230712 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2022-10-11 | GSE212438 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2023-04-25 | GSE218685 | GEO