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Prdm16 regulation of Shh-Gli1-Hoxc4 signaling is required for Granule Neuron Progenitor expansion and cerebellar related behavior

ABSTRACT: Purpose:To gain a deeper insight into how Prdm16 regulates cerebellar development, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by Prdm16 deletion at P3. Methods: Total RNA was extracted from P3 cerebellar tissue of Prdm16 cKO and Prdm16fl/fl mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the Prdm16fl/fl and Prdm16 cKO cerebellum, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to regulation of glial cell differentiation and forebrain development, and cerebellum development. Up-regulated genes showed a significant enrichment of terms involved in negative regulation of cell differentiation. These results reflected the importance of Prdm16 in cerebellar development. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how Prdm16 gene contribute to cerebellar development.

ORGANISM(S): Mus musculus

PROVIDER: GSE134091 | GEO | 2019/07/11

REPOSITORIES: GEO

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Apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state

Project description:Through their biased localization and function within the cell, polarity complex proteins are necessary to establish the cellular asymmetry required for tissue organization. Well-characterized germinal zones, mitogenic signals, and cell types make the cerebellum an excellent model for addressing the critical function of polarity complex proteins in the generation and organization of neural tissues. Deleting apical polarity complex protein Pals1 in the developing cerebellum results in a remarkably undersized cerebellum with disrupted layers in poorly formed folia and strikingly reduced granule cell production. We demonstrate that Pals1 is not only essential for cerebellum organogenesis, but also for preventing premature differentiation and thus maintaining progenitor pools in cerebellar germinal zones, including cerebellar granule neuron precursors (CGNP) in the external granule layer (EGL). In the Pals1 mutants, expression of genes that regulate cell cycle were diminished, correlating with the loss of proliferating population of germinal zones. Furthermore, enhanced Shh signaling through activated Smoothened (Smo) cannot overcome impaired cerebellar cell generation, arguing for an epistatic role of Pals1 in proliferation capacity. Our study identifies Pals1 as a new intrinsic factor that regulates the generation of cerebellar cells and Pals1 deficiency as a potential inhibitor of overactive mitogenic signaling. Two groups of samples are included: mRNA obtained from 4 WT and 4 CKO animals at E17.5. hGFAP-Cre mice was used to delete Pals1 from most cerebellar neurons and glia (termed Pals1 CKO). Pals1fl/fl and hGFAP-Cre (Zhuo et al., 2001) were bred for generation of CKO.

2016-06-30 | E-GEOD-75696 | biostudies-arrayexpress

PRDM16 orchestrates neuron-vascular communication for angiogenesis during brain development

Project description:Purpose:To gain a deeper insight into how PRDM16 regulates neuron-vascular communication for angiogenesis, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by PRDM16 deletion at E15. Methods: Total RNA was extracted from E15 telencephalic tissue of Prdm16cKO and Prdm16fl/fl mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the Prdm16fl/fl and Prdm16cKO brain cortex, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to neurogenesis, blood vessel development and secretion by cells. Up-regulated genes showed a significant enrichment of terms involved in negative regulation of cell communication and negative regulation of angiogenesis. These results reflected the importance of PRDM16 in cortical development. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how Prdm16 gene contribute to brain cortical development.

2019-05-08 | GSE130802 | GEO

H2AZ Orchestrates Neural Progenitor Cell Proliferation and Differentiation via Setd2-mediated H3K36me3 Modification [RNA-seq]

Project description:Purpose:To gain a deeper insight into how H2AZ regulates embryonic neurogenesis, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by H2AZ deletion at E12. Methods: Total RNA was extracted from E12 telencephalic tissue of H2AZcKO and H2AZfl/fl mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the H2AZfl/fl and H2AZcKO brain, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to transcription and cortex development, such as regulation of transcription, cerebellar cortex formation, forebrain development, and cerebellum development. Up-regulated genes showed a significant enrichment of terms involved in negative regulation of cell differentiation, neuron migration, and cognition. These results reflected the importance of H2AZ in cortical development. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how a disruption in the H2AZ gene may contribute to cortical development.

2017-05-29 | GSE99347 | GEO

Expression analysis of cerebellar granular cell layer isolated from PTEN conditional null mutants and controls

Project description:A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination was identified in mice that conditionally lack PTEN in cerebellar granular cells (PTEN cKO) Expression analysis was performed with RNA obtained selectively from cerebellar granular cell layer of PTEN conditional null mutants and controls

2016-09-30 | GSE80966 | GEO

Gene expression signature of cerebellum hypoplasia in a mouse model of Down syndrome (Part I).

Project description:We designed a large scale gene expression study in Ts1Cje mice between P0 and P10 in order to measure the effects of trisomy 21 on a large number of samples (56 in total) in a tissue that is affected in Down syndrome (the cerebellum) and to quantify the defect during development in order to correlate gene expression changes to the phenotype observed. Keywords: Down syndrome, Ts1Cje, cerebellum, development, hypoplasia We analyzed gene expression in the cerebellum of Ts1Cje and euploid mice at P0, P3, P7 and P10 using pangenomic two colors microarrays containing 25 344 probes representing approximately 15 574 mouse genes. 56 samples from individual cerebellum were hybridized on 28 microarrays. On each microarray we hybridized a Ts1Cje sample versus an euploid sample and always a male versus a female. In addition on the same microarray we always compared samples from mice of the same age or with a maximum difference of 4 days (P0 versus P3, P3 versus P7 or P7 versus P10).

2009-03-31 | E-GEOD-11448 | biostudies-arrayexpress

H2A.Z Regulates Astrocyte Proliferation and Differentiation via H3K56ac Modification

Project description:Purpose:To gain a deeper insight into how H2A.Z regulates astrocytogenesis, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by H2AZ deletion at E16. Methods: Total RNA was extracted from E16 telencephalic tissue of H2A.ZcKO and H2A.Zfl/fl mice. Then total RNA was quality controlled and quantified using an Agilent 2100 Bioanalyzer. After converting to cDNA and building library, high-throughput sequencing was performed using the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately approximately one thousand transcripts showed differential expression between the H2A.Zfl/fl and H2A.ZcKO brain, with a fold change ≥1.5 and p value <0.05. Gene ontology (GO) analysis showed that the down-regulated genes were enriched in the terms related to regulation of glial cell differentiation and forebrain development, and cerebellum development. Up-regulated genes showed a significant enrichment of terms involved in negative regulation of cell differentiation. These results reflected the importance of H2A.Z in cortical development. Conclusions: We conclude that RNA-seq based transcriptome characterization would provide a framework for understanding how H2A.Z gene contribute to cortical development.

2017-07-28 | GSE101939 | GEO

Gene expression data from mouse cerebellar tumor samples

Project description:Gene expression data from mouse cerebellar tumors generated using CRISPR/Cas9 technology to disrupt Ptch1 and Chd7 in the embryonic cerebellum of Chd7 fl/+ mice by in utero electroporation.

2018-08-24 | GSE72331 | GEO

A peptidomic approach to characterize peptides involved in cerebellar cortex development leads to the identification of the neurotrophic effects of nociceptin

Project description:The cerebellum is a brain structure involved in motor and cognitive functions. The development of the cerebellar cortex (the external part of the cerebellum) is under the control of numerous factors. Among these factors, neuropeptides including PACAP or somatostatin modulate the survival, migration and/or differentiation of cerebellar granule cells. Interestingly, such peptides contributing to cerebellar ontogenesis usually exhibit a specific transient expression profile with a low abundance at birth, a high expression level during the developmental processes, which take place within the first two postnatal weeks in rodents, and a gradual decline toward adulthood. Thus, to identify new peptides transiently expressed in the cerebellum during development, rat cerebella were sampled from birth to adulthood, and analyzed by a semi-quantitative peptidomic approach. A total of 33 peptides were found to be expressed in the cerebellum. Among these 33 peptides, 8 had a clear differential expression pattern during development, 4 of them i.e. cerebellin 2, nociceptin, somatostatin and VGF [353-372], exhibiting a high expression level during the first two postnatal weeks followed by a significative decrease at adulthood. A focus by a genomic approach on nociceptin, confirmed that the precursor mRNA is transiently expressed during the first week of life in granule neurons within the internal granule cell layer of the cerebellum, and showed that the nociceptin receptor is also actively expressed between P8 and P16 by the same neurons. Finally, functional studies revealed a new role for nociceptin, acting as a neurotrophic peptide able to promote the survival and differentiation of developing cerebellar granule neurons.

2018-06-15 | PXD006874 | Pride

PC transcriptome

Project description:During the first 10 postnatal days of mouse development, Purkinje cells, neurons of the cerebellum, pass through different developmental processes of differentiation such as profound dendritic remodeling and growth, cell death and loss of their ability to regenerate their axons. To identify the genes involved in these different processes and in particular transcription factors, the gene expression patterns of murine cerebellar cortical area centered on Purkinje soma have been measured using Affymetrix microarrays at 5 different developmental stages (postnatal days P0, P3, P5, P7 and P10; 4 replicates = 4 independent measurements for each stage).

2012-03-15 | E-MEXP-3444 | biostudies-arrayexpress

RNA-seq Analysis of Wild Type and Ptpn11-deficient cerebellar Transcriptomes

Project description:We have recently discovered that deletion of Ptpn11, which codes for protein tyrosine phosphatase Shp2, blocks Bergmann glia (BG) formation and cerebellar foliation, whereas expressing a constitutively active Mek1 (Map2k1), Mek1DD, reverses the Ptpn11-deficient phenotypes, uncovering a previously unappreciated role of BG in folding of the cerebellar cortex. Relatively little is known regarding to the BG induction. The goal of the study was to determine molecular features of newly generated BG. To identify transcripts enriched in nascent BG, we performed RNA-seq of microdissected cerebellar tissues from wild type (WT), En1cre/+;Ptpn11F/F (Ptpn11-cKO), and En1cre/+;Ptpn11F/F;R26Mek1DD/+ (Ptpn11-cKO;MEK) embryos at E12.5, E13.5, and E14.5. As BG are initially formed at E13.5, we reasoned that BG-enriched transcripts should be increased from E12.5 to E14.5, decreased in Ptpn11-cKO cerebella, and restored in Ptpn11-cKO;MEK cerebella. By intersecting differentially expressed (DE) genes based on the above-mentioned assumptions, we wanted to identify genes that are specifically expressed in BG and affected by Ptpn11 deletion. Conclusions: though RNA-seq and subsequent validation, we have successfully identified genes that enriched in nascent BG in the developing mouse cerebellum.

2017-05-10 | GSE87104 | GEO

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