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Chronic Crebbp knockout in cerebellar granule neuron precursors [development]

ABSTRACT: Chronic Crebbp knockout in cerebellar granule neuron precursors [development]

PROVIDER: PRJNA419444 | ENA |

REPOSITORIES: ENA

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Chronic Crebbp knockout in cerebellar granule neuron precursors [development]

Project description:Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic Hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mutations of CREBBP. By contrast, loss of Crebbp in GNPs during postnatal development synergizes with oncogenic activation of SHH signaling to drive MB growth, thereby explaining the enrichment of somatic CREBBP mutations in SHH MB of adult patients. Together, our data provide novel insights into time-sensitive consequences of CREBBP mutations and corresponding associations with human diseases. We used microarrays to detail the global programme of gene expression underlying the knockout of Crebbp in murine granule neuron precursors, chronically induced at embryonic stages of development.

2017-11-22 | GSE107252 | GEO

The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

Project description:Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional knockout of the transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal mouse brain. In laser capture microdissection followed by RNASeq, designed to profile gene expression specifically in the external granule layer (EGL) of the cerebellum, we find that SnoN promotes the expression of cell proliferation genes and concomitantly represses differentiation genes in granule neuron precursors in vivo. Remarkably, bioinformatics analyses reveal that SnoN-regulated genes contain binding sites for the transcription factors N-myc and Pax6, which promote the proliferation and differentiation of granule neuron precursors, respectively. Accordingly, we uncover novel physical interactions of SnoN with N-myc and Pax6 in cells. In behavior analyses, conditional knockout of SnoN impairs cerebellar-dependent learning in a delayed eye-blink conditioning paradigm, suggesting that SnoN-regulation of granule neuron precursor proliferation bears functional consequences at the organismal level. Our findings define a novel function and mechanism for the major transcriptional regulator SnoN in the control of granule neuron precursor proliferation in the mammalian brain.

2018-12-10 | GSE120276 | GEO

The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

2018-12-10 | GSE120278 | GEO

Identification of genes expressed with temporal-spatial restriction to developing cerebellar neuron precursors by a functional genomic approach perspective of human cancers.

Project description:Swiss-Webster B mouse postnatal day 4-5 primary cerebellar culture (pooled from litter mates) treated with sonic hedgehog (Shh), controls (veh), growth arrested (arrest), cycloheximide (cyc) for 1, 3 and 24 hours. Different treatment conditions with biological replicates. Mouse cerebellar granule cell neuron precursors under different treatment conditions.

2013-09-06 | E-GEOD-50606 | biostudies-arrayexpress

WDR4 conditional knockout in mouse cerebellar granule progenitors for proteome analysis

Project description:To uncover candidates which are WDR4 downstream effectors regulating cerebellar granule neuron proliferation phenotype, we utilized quantitative proteomics analysis (TMT labeling) with granule neuron progenitors from P7 wdr4 conditional knockout (using Atoh1-Cre) and control cerebella.

2023-03-11 | PXD022319 | Pride

The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

Project description:The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

| PRJNA492389 | ENA

The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

Project description:The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

| PRJNA492392 | ENA

The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

Project description:The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain

| PRJNA492391 | ENA

The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation

Project description:The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation

| PRJNA503865 | ENA

scRNA-seq study of Eed-deleted cerebellar granule neuron progenitors (CGNPs)

Project description:scRNA-seq study of Eed-deleted cerebellar granule neuron progenitors (CGNPs)

| PRJNA855640 | ENA