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Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development

ABSTRACT: Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development

PROVIDER: PRJNA575159 | ENA |

REPOSITORIES: ENA

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Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development

Project description:The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype.

2020-01-21 | GSE138227 | GEO

Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development [cdkn1c_KO]

2020-01-21 | GSE138228 | GEO

Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development [Cdkn1c_allelic expression]

2019-12-03 | GSE138229 | GEO

Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development

Project description:Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development

| PRJNA575163 | ENA

Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development [cdkn1c_KO]

Project description:Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development [cdkn1c_KO]

| PRJNA575162 | ENA

Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development [Cdkn1c_allelic expression]

Project description:Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development [Cdkn1c_allelic expression]

| PRJNA575164 | ENA

Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development.

Project description: Not available

| S-EPMC6954230 | biostudies-literature

Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-03 | GSE138230 | GEO

Imprinted DNA methylation reconstituted at a non-imprinted locus

Project description:Background: In mammals, tight regulation of cytosine methylation is required for embryonic development and cellular differentiation. The trans-acting DNA methyltransferases that catalyze this modification have been identified and characterized; however, these proteins lack sequence specificity, leaving the mechanism of targeting unknown. A cis acting regulator within the Rasgrf1 imprinting control region (ICR) is necessary for establishment and maintenance of imprinted methylation at the locus. Here we investigate whether 3kb of sequence from the Rasgrf1 ICR is sufficient to direct appropriate imprinted methylation and target-gene expression patterns when ectopically inserted at the Wnt1 locus. Results: The Rasgrf1 ICR at Wnt1 lacked somatic methylation when maternally transmitted, and was fully methylated upon paternal transmission, consistent with its behavior at the Rasgrf1 locus. It was unmethylated in the female germline and was enriched for methylation in the male germline, though not to the levels seen at the endogenous Rasgrf1 allele. Wnt1 expression was not imprinted by our construct, likely due to additional sequences being required for this function. Conclusion: We have identified sequences that are sufficient for partial establishment and full maintenance of the imprinted DNA methylation patterns. Because full somatic methylation can occur without full gametic methylation, we infer that somatic methylation of the Rasgrf1 ICR is not simply a consequence of maintained gametic methylation.

2016-09-12 | GSE79895 | GEO

Knockdown of CDKN1C (p57kip2) and PHLDA2 results in developmental changes in bovine pre-implantation embryos

Project description:Transcriptome of CDKN1C-siRNA-injected embryos were compared to sham-injected embryos using RNA-sequencing to determine the genes and pathways downstream of the silenced gene that may have been altered. Transcriptome comparison between two pools of embryos (i.e. CDKN1C-siRNA-injected vs sham-injected embryos)

2012-12-15 | E-GEOD-42931 | biostudies-arrayexpress

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