Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA377428 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5298328.fastq.gz | Fastqsanger.gz | |||
| SRR5298329.fastq.gz | Fastqsanger.gz |
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Project description:The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex. Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation. We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice
2013-03-19 | E-GEOD-35260 | biostudies-arrayexpress
Project description:The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using lens and forebrain chromatin from mice. A total of 3,723 (forebrain) and 3,514 (lens) Pax6-containing peaks were identified, with ~70% of them found in both tissues and thereafter called “common” peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, -PD/HD and -HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit control via components of FGF (Fgfr2, Ccnd1, and Prox1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis. Examination of Pax6 in mouse embryonic forebrain and newborn lens. We performed ChIP-seq on mouse E12.5 embryonic forebrain and newborn lens. Genome-wide binding sites of Pax6, H3K4me1, H3K4me3, H3K27ac, H3K27me3, and Pol2 were generated. We also performed RNA-seq on mouse E12.5 embryonic forebrain and newborn lens epithelial cells and fibers.
2015-07-09 | E-GEOD-66961 | biostudies-arrayexpress
Project description:Individuals with Down syndrome (DS, Ts21) have impaired neurogenesis during development. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we carried out single cell RNA-sequencing of Ts21 interneuron progenitors .
2022-07-18 | GSE201523 | GEO
Project description:The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex. Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation.
2013-03-19 | GSE35260 | GEO
Project description:Pax6 is one of the important transcription factors involved in regional specification and neurogenesis in the developing cortex. To identify candidate target genes of Pax6, we performed transcriptome analyses of wild-type (WT) and Pax6 homozygous mutant rats (rSey2/rSey2) telencephalons at E11.5 within a day of onset of Pax6 expression. In our transcriptome analyses, down-regulated genes in the rSey2/rSey2 rat exhibited larger fold changes, whereas up-regulated genes had relatively small fold changes.
2013-01-11 | GSE43413 | GEO
Project description:Pax6 is one of the important transcription factors involved in regional specification and neurogenesis in the developing cortex. To identify candidate target genes of Pax6, we performed transcriptome analyses of wild-type (WT) and Pax6 homozygous mutant rats (rSey2/rSey2) telencephalons at E11.5 within a day of onset of Pax6 expression. In our transcriptome analyses, down-regulated genes in the rSey2/rSey2 rat exhibited larger fold changes, whereas up-regulated genes had relatively small fold changes. Total RNA was prepared using from 13 telencephalon dissected from E11.5 WT or rSey2/rSey2 rats embryos. Experiments using 13 telencephaon were repeated twice in each genotype.
2013-01-11 | E-GEOD-43413 | biostudies-arrayexpress
Project description:The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. However the molecular logic of neurogenic fate determination is still ill understood, even though some key transcription factors have been implicated. Here we describe how one of these, the transcription factor Pax6, regulates adult neurogenesis by initiating a cross-regulatory network of 3 transcription factors executing neuronal fate and regulating genes required for neuronal differentiation. This network is initiated and driven to sufficiently high expression levels by the transcription factor Pax6 in close interaction with Brg1-containing SWI/SNF chromatin remodeling factors. Genetic deletion of either Pax6 or Brg1, the ATPase unit of the SWI/SNF complex, in neural stem cells of the adult mouse subependymal zone results in a fate conversion to distinct glial subtypes most pronounced when neuroblasts leave the neurogenic niche. Consistent with the phenocopy in vivo virtually all genes down-regulated by Brg1 deletion have Pax6-binding motifs. Amongst the few down-stream transcription factors are Sox11, Nfib and Brn4 that crossregulate each other and rescue neurogenesis also in direct reprogramming in the absence of Brg1 (or Pax6). Thus the function of Pax6-SWI/SNF is necessary and sufficient for neuronal fate maintenance and initiates a cross-regulatory effector network required for neuronal fate execution and maintenance to counteract glial differentiation in the adult brain. This identifies a novel role highly specific role of a chromatin-remodelling complex in stabilizing fate decisions in normal and forced neurogenesis. We performed gene expression microarray analysis on tissue derived from the SEZ or from the core region of the olfactory bulb from Brg1 cKO and control mice
2013-08-01 | E-GEOD-39362 | biostudies-arrayexpress