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Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal.

ABSTRACT: The expansion of the neocortex during mammalian brain evolution results primarily from an increase in neural progenitor cell divisions in its two principal germinal zones during development, the ventricular zone (VZ) and the subventricular zone (SVZ). Using mRNA sequencing, we analyzed the transcriptomes of fetal human and embryonic mouse VZ, SVZ and cortical plate (CP). We describe sets of genes that are up- or down-regulated in each germinal zone. These data suggest that cell adhesion and cell-extracellular matrix (ECM) interactions promote the proliferation and self-renewal of neural progenitors in the developing human neocortex. Notably, relevant ECM-associated genes include distinct sets of collagens, laminins, proteoglycans and integrins, along with specific sets of growth factors and morphogens. Our data establish a basis for identifying novel cell-type markers and open up avenues to unravel the molecular basis of neocortex expansion during evolution. Total RNA was isolated from the VZ, inner SVZ (ISVZ), outer SVZ (OSVZ) and CP of six 13-16 weeks post-conception (w.p.c.) human fetuses and from the VZ, SVZ and CP of five E14.5 mouse embryos using laser capture microdissection of Nissl-stained cryosections of dorsolateral telencephalon. Poly A+ RNA was used as template for the preparation of cDNA which were then subjected to single-end 76-bp RNA-Seq.

ORGANISM(S): Homo sapiens

SUBMITTER: Martin Kircher

PROVIDER: E-GEOD-38805 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal.

Project description:The expansion of the neocortex during mammalian brain evolution results primarily from an increase in neural progenitor cell divisions in its two principal germinal zones during development, the ventricular zone (VZ) and the subventricular zone (SVZ). Using mRNA sequencing, we analyzed the transcriptomes of fetal human and embryonic mouse VZ, SVZ and cortical plate (CP). We describe sets of genes that are up- or down-regulated in each germinal zone. These data suggest that cell adhesion and cell-extracellular matrix (ECM) interactions promote the proliferation and self-renewal of neural progenitors in the developing human neocortex. Notably, relevant ECM-associated genes include distinct sets of collagens, laminins, proteoglycans and integrins, along with specific sets of growth factors and morphogens. Our data establish a basis for identifying novel cell-type markers and open up avenues to unravel the molecular basis of neocortex expansion during evolution.

2012-07-03 | GSE38805 | GEO

The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

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

The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

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

Chromatin Accessibility in Developing Human Brain

Project description:<p>Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>

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Single-cell RNA-seq (10X Genomics Chromium) of LGE, MGE, CGE, and Cortex from mouse embryonic forebrain

Project description:We performed single-cell RNA sequencing to characterize transcriptional heterogeneity of neural progenitors within the ventricular zone and subventricular zone of E12.5 and E14.5 mouse cortex and ganglionic eminences. By using a transgenic mouse line (Nestin-d4-Venus) to enrich for VZ cells, we detect significant transcriptional heterogeneity within VZ and SVZ progenitors, both between forebrain regions and within spatial subdomains of specific GEs.

2022-02-28 | GSE190593 | GEO

Extracellular matrix components HAPLN1, lumican and collagen I cause hyaluronic acid-dependent folding of the developing human neocortex

Project description:Neocortical expansion, thought to underlie the cognitive traits unique to humans, is accompanied by cortical folding. This folding starts around gestational week (GW) 20, but what causes it remains largely unknown. Extracellular matrix (ECM) has been previously implicated in neocortical expansion. Here, we investigate the potential role of ECM in the formation of neocortical folds. We focus on three specific ECM components localized in the human fetal cortical plate (CP): hyaluronan and proteoglycan link protein 1, lumican and collagen I (collectively, HLC). Addition of HLC to cultures of human fetal neocortex (11-22 GW) caused local changes in tissue stiffness and induced CP folding. HLC-induced folding increased CP hyaluronic acid (HA), required the HA-receptor CD168 and downstream ERK signaling, and was prevented/reversed by hyaluronidases. HLC did not induce CP folding in cultures of developing mouse and ferret neocortex. Together, our data suggest a human-specific role of ECM in neocortical folding.

2018-06-27 | GSE106640 | GEO

Novel primate miRNAs co-evolved with ancient target genes in germinal zone specific expression patterns [RISC trap immunoprecipitation]

Project description:Major non primate-primate differences in corticogenesis include the dimensions, precursor lineages and developmental timing of the germinal zones (GZ). microRNAs (miRNAs) of laser dissected GZ compartments and cortical plate (CP) from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ including Ventricular Zone (VZ), outer and inner subcompartments of the Outer SubVentricular Zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs present in primate, but absent in rodent, contributed disproportionately to the differential expression between GZ sub-regions. Prominent among the validated targets of these miRNAs were cell-cycle and neurogenesis regulators. Co-evolution between the emergent miRNAs and their targets suggested that novel miRNAs became integrated into ancient gene circuitry to exert additional control over proliferation. We conclude that multiple cell-cycle regulatory events contribute to the emergence of primate-specific cortical features, including the OSVZ, generated enlarged supragranular layers, largely responsible for the increased primate cortex computational abilities. target mRNAs for selected miRNAs were detected with RISC trap immunoprecipitation

2014-02-27 | E-GEOD-52607 | biostudies-arrayexpress

Expression profiles of Ecrg4hetero beta-gal positive neurosphere and Ecrg4hetero beta-gal positive VZ/SVZ

Project description:To find factors that increase and decrease in VZ/SVZ

2019-02-27 | GSE120626 | GEO

Dnmt3a-dependent non-promoter DNA methylation facilitates transcription of neurogenic genes

Project description:This SuperSeries is composed of the following subset Series: GSE22473: Murine postnatal subventricular zone (SVZ) neural stem cells (NSCs): Wild-type (WT) vs. Dnmt3a-null (KO) GSE22474: Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [Agilent] GSE22475: Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [NimbleGen] Refer to individual Series

2010-06-24 | E-GEOD-22476 | biostudies-arrayexpress

Novel primate miRNAs co-evolved with ancient target genes in germinal zone specific expression patterns [miRNA-Seq]

Project description:Major non primate-primate differences in corticogenesis include the dimensions, precursor lineages and developmental timing of the germinal zones (GZ). microRNAs (miRNAs) of laser dissected GZ compartments and cortical plate (CP) from embryonic E80 macaque visual cortex were deep sequenced. The CP and the GZ including Ventricular Zone (VZ), outer and inner subcompartments of the Outer SubVentricular Zone (OSVZ) in area 17 displayed unique miRNA profiles. miRNAs present in primate, but absent in rodent, contributed disproportionately to the differential expression between GZ sub-regions. Prominent among the validated targets of these miRNAs were cell-cycle and neurogenesis regulators. Co-evolution between the emergent miRNAs and their targets suggested that novel miRNAs became integrated into ancient gene circuitry to exert additional control over proliferation. We conclude that multiple cell-cycle regulatory events contribute to the emergence of primate-specific cortical features, including the OSVZ, generated enlarged supragranular layers, largely responsible for the increased primate cortex computational abilities. Seven brain regions (VZ17, OSVZ17int, OSVZ17ext, CP17, VZ18, OSVZ18, CP18). OSVZ17int corresponds to the inner (apical) third of OSVZ 17 and OSVZ17ext to the most outer (basal) third of OSVZ 17, located immediately below the Outer Fiber Layer (Smart et al., 2002; Betizeau et al., 2013)

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