Genetic and microstructural differences in the cortical plate of gyri and sulci during gyrification in fetal sheep
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ABSTRACT:
PROVIDER: PRJNA592896 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10573373.fastq.gz | Fastqsanger.gz | |||
| SRR10573374.fastq.gz | Fastqsanger.gz | |||
| SRR10573375.fastq.gz | Fastqsanger.gz | |||
| SRR10573376.fastq.gz | Fastqsanger.gz | |||
| SRR10573377.fastq.gz | Fastqsanger.gz |
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Project description:Gyrification of the cerebral cortex is a developmentally important process, however the mechanisms that drive cortical folding remain unknown. Theories propose that changes within the cortical plate (CP) cause gyrification, yet differences between the CP below gyri and sulci have not been investigated. Here we report genetic and microstructural differences in the CP below gyri and sulci assessed before (gestational age (GA) 70), during (GA 90) and after (GA 110) gyrification in fetal sheep. The areal density of BDNF-, CDK5-, and NeuroD6-immunopositive cells were increased, and HDAC5 and MeCP2 mRNA levels were decreased, in the CP below gyri compared to sulci during gyrification, but not before. Only the areal density of BDNF-immunopositive cells remained increased after gyrification. MAP2-immunoreactivity was also increased in the CP below gyri compared to sulci at GA 90, and this was associated with microstructural changes assessed via neurite orientation dispersion and density imaging (NODDI) at GA 98. Differential neurite outgrowth may therefore be a strong candidate to explain local changes in CP architecture during gyrification.
2019-12-03 | GSE141233 | GEO
Project description:Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we find that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 results in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 results in enhanced formation of gyri. Single cell transcriptomics and simulations suggest that changes in adhesive properties of cortical neurons, their proportions and densities in the cortical plate, combined with lateral dispersion during their radial migration are important folding parameters. These results identify key developmental mechanisms that cooperate to promote cortical gyrification
2025-05-20 | GSE267391 | GEO
Project description:The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 ? Eomes ? Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism. To determine the role of Eomes in the propagation of the protomap to cortical plate neurons, used microarray analysis of E14.5 cortex from five wild type and three Eomes knockout mice.
2013-04-02 | E-GEOD-43387 | biostudies-arrayexpress
Project description:Mammalian brain evolved through several transitions between gyrencephaly and lissencephaly. Mechanisms generating gyrified or smooth brain are incompletely understood. Here we demonstrate that a short embryonic pulse of activating mutations in Pik3ca, the catalytic subunit of PI3K enzyme is sufficient to cause mouse cortical gyrification. We demonstrate that this gyrification phenotype is initiated by subtle focal regulation of apical cell adhesion and proliferation via PI3K-dependent localization of Yap protein. Treatment with verteporfin (Drug) a nuclear Yap inhibitor, attenuated over-proliferation and adhesion abnormalities, and subsequently gyrification. The purpose of this study was to compare the control and mutant mouse transcriptome, and their respective effect upon verteprofin treatment.
2019-05-15 | GSE127896 | GEO
Project description:The regional specification of the cerebral cortex can be described by protomap and protocortex hypotheses. The protomap hypothesis suggests that the regional destiny of cortical neurons and the relative size of the cortical area are genetically determined early during embryonic development. The protocortex hypothesis suggests that the regional growth rate is predominantly shaped by external influences. In order to determine regional volumes of cortical compartments (cortical plate (CP) or subplate (SP)) and estimate their growth rates, we acquired T2-weighted in utero MRIs of 40 healthy fetuses and grouped them into early (<25.5 GW), mid- (25.5-31.6 GW), and late (>31.6 GW) prenatal periods. MRIs were segmented into CP and SP and further parcellated into 22 gyral regions. No significant difference was found between periods in regional volume fractions of the CP or SP. However, during the early and mid-prenatal periods, we found significant differences in relative growth rates (% increase per GW) between regions of cortical compartments. Thus, the relative size of these regions are most likely conserved and determined early during development whereas more subtle growth differences between regions are fine-tuned later, during periods of peak thalamocortical growth. This is in agreement with both the protomap and protocortex hypothesis.
| S-EPMC7325717 | biostudies-literature
Project description:The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 → Eomes → Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.
2013-04-02 | GSE43387 | GEO
Project description:study investigating the initiation of systemic inflammatory signaling in fetuses exposed to TLR-4 agonist lipopolysaccharides from E.coli microarray was used to determine the inflammatory transcriptome in circulating fetal immunocytes fetal sheep at 92d GA were catheterised prior to intraamniotic exposure fo saline or lipopolysaccharides for 48h prior to euthanasia
2015-08-21 | E-GEOD-72240 | biostudies-arrayexpress
Project description:Background: Genomic imprinting is an epigenetic phenomenon of differential allelic expression based on parental origin. To date a total of 255 imprinted genes have been identified or predicted among all investigated mammal species. However, only 21 have been described in sheep and 11 are annotated in current ovine genome. Results: Here we aim to use DNA/RNA throughput sequencing to identify monoallelically expressed and imprinted genes in organs of day 135 fetal sheep, and 2) to determine whether different levels of maternal energy intake (100% of NRC energy requirement or control, 140% or over-, and 60% or under-fed) influence genomic imprinting. We report strategies to solve technical challenges in the next-generation sequencing data analysis pipeline, including alignment bias of RNA sequencing reads and filtering potential false positives. We identified 80 monoallelically expressed and 18 putatively imprinted genes using the list of 255 stated above as a guide. Five (45.6% of 11) were already known imprinted genes in sheep, the other 13 were known imprinted in other mammals. Sanger sequencing confirmed four putative sheep imprinted genes INPP5F, PLAGL1, CASD1 and PPP1R9A. Among the 13 putative imprinted genes, five localized in the known sheep imprinting clusters of MEST domain on chromosome 4, DLK1/GTL2 domain on chromosome 18 and IGF2/H19 domain on chromosome 21, three were in a novel sheep imprinted cluster on chromosome 4 known in other species as PEG10/SGCE. Additionally, we found that the imprinted genes PHLDA2, SLC22A18, DIRAS3, and IGF2 were differentially expressed, albeit without allelic expression reversal, among the three maternal nutritional groups. Conclusions: Together, our results expanded the sheep imprinted gene list to 34 and demonstrated the influence of maternal diet on fetal imprinting under the conditions studied.
2018-08-29 | GSE111306 | GEO
Project description:PI3K-Yap activity drives cortical gyrification and hydrocephalus in mice
| PRJNA525718 | ENA
Project description:We report the application of High throughout sequencing to explore the differences of skin between Super Merino sheep(SM) and Small Tail Han sheep, which have remarkable phenotype differences on wool and hair follicle traits. We analysed the expression data by CLC genomic workbench 9.0 software. We find there are 435 differential expressional genes (DEGs) (127 were up-regulated and 308 were down-regulated) when STH sheep as control group. Some hair follicle KRTs, KAPs genes and hair follicle stem cells marker genes, were up-regulated in SM sheep. However, some of mammalian epidermal development complex (EDC) family genes were up-regulated in STH sheep. The GO and gene network analysis shown high expression genes in SM sheep enriched on type I interferon, lipid/fatty acid synthesis metabolism. This study provide more details in skin which control the development of follicle and wool in sheep.
2017-11-16 | GSE95785 | GEO