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SRP029912
Mus musculus
27 Downloadable Samples
Illumina HiSeq 2500
Description
Precise spatiotemporal control of mRNA translation machinery is essential to proper development of highly complex systems like the neocortex. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of the initiation and elongation factors of the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some of the HuR-dependent proteins, the association with polysomes depends on the eIF2 alpha kinase 4 (eIF2ak4), which associated with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR prior to embryonic day 10 (E10) disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity. Overall design: Cortex was dissected from WT and HuR cKO mouse pups at embryonic day 13 (E13) or the day of birth (P0).
Publication Title
Thalamic WNT3 Secretion Spatiotemporally Regulates the Neocortical Ribosome Signature and mRNA Translation to Specify Neocortical Cell Subtypes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem cell commitment during neurogenesis. “LncRNAs control neurogenesis” Aprea, Prenninger, Dori, Monasor, Wessendof, Zocher, Massalini, Ghosh, Alexopoulou, Lesche, Dahl, Groszer, Hiller, Calegari, The EMBO Journal (In Press) Overall design: mRNA profiles of Proliferating Progenitors, Differentiating Progenitors and Neurons from lateral cortex of E14.5 mouse embryos. Each cell type in three biological replicates.
Publication Title
Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNAs establish robustness and adaptability of a critical gene network to regulate progenitor fate decisions during cortical neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined mRNA expression profiles using mouse mRNA microarray (Illumina MouseWG-6 v2). Comparison of E13 and E16 mRNA expression profiles allowed us to identify regulatory gene networks for maintaining stage specific homeostasis of BPs throughout neurogenesis.
Publication Title
MicroRNAs establish robustness and adaptability of a critical gene network to regulate progenitor fate decisions during cortical neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Purpose: Foxp2 is the first and for now the only gene connected to speech and language in humans. Two aminoacid substitutions took place in this protein during recent human evolution, after our split from the last common ancestor with chimpanzees, and are most likely to have undergone positive selection in human lineage (Enard et al., 2002). Methods: Transgenic mice in which the wild-type (murine) version of Foxp2 was replaced with the one bearing two human-specific amino acid substitutions (i.e. "humanized" Foxp2) - Foxp2hum/hum, have been compared to their wild-type (WT) counterparts in terms of behavior, electrophysiology and striatal gene expression. The latter was analyzed through RNA-sequencing performed on pooled indexed libraries on three flow cells on Illumina GAIIx. The reads were mapped to mouse genome (mm9) by TopHat 1.4.1 and were counted using Bedtools. mRNA profiles were obtained with more than 20 million reads for every sample. Differential gene expression was analyzed with DESeq using multifactor model (Anders and Huber, 2010). Results: Wild-type and Foxp2hum/hum mice did not show any significant differences in expression at individual gene level, neither in dorsomedial nor in dorsolateral striatum. However, when genes were grouped into functional categories and analyzed accordingly, this revealed a significant downregulation of functional categories related to synaptic signalling and plasticity in dorsomedial striatum of Foxp2hum/hum mice. Overall design: RNA-sequencing was performed on dorsomedial and dorsolateral striatum of wild-type and Foxp2hum/hum mice, on three flow cells Illumina GAIIx. The libraries from each sample were indexed and pooled together.
Publication Title
Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET triple knockdown cells to control cells treated with non-targeting siRNAs to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. (
Publication Title
Transcription factor Sp3 knockout mice display serious cardiac malformations.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 24 Downloadable Samples
- IlluminaHiSeq2500, NextSeq500
Description
Using zebrafish tet2-/-;tet3-/- mutants, we identify functions for Tet enzymes and 5-hydroxymethylcytosine (5hmC) in regulating gene expression and cell type-specific differentiation during retinal development. Overall design: RNAseq from tet2-/-;tet3-/- mutant and sibling embryonic eye tissues dissected at 72hpf and 36hpf.
Publication Title
Tet-mediated DNA hydroxymethylation regulates retinal neurogenesis by modulating cell-extrinsic signaling pathways.
Sample Metadata Fields
No sample metadata fields
View Samples