Multiple parallel cell lineages in the developing mammalian cerebral cortex
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA980720 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22508200_1.fastq.gz | Fastqsanger.gz | |||
| SRR22508200_2.fastq.gz | Fastqsanger.gz | |||
| SRR22508201_1.fastq.gz | Fastqsanger.gz | |||
| SRR22508201_2.fastq.gz | Fastqsanger.gz | |||
| SRR22508202_1.fastq.gz | Fastqsanger.gz |
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Project description:Cortical neurogenesis follows a simple lineage: apical Radial Glia Cells (RGC) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, like human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret, and barcoded lineage tracking, to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not mouse. Neurons followed parallel differentiation trajectories in gyrus and sulcus, with different expression of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex. This SuperSeries is composed of the SubSeries listed below.
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Project description:Cortical neurogenesis follows a simple lineage: apical radial glia cells (RGCs) generate basal progenitors, and these produce neurons. How this occurs in species with expanded germinal zones and a folded cortex, such as human, remains unclear. We used single-cell RNA sequencing from individual cortical germinal zones in ferret and barcoded lineage tracking to determine the molecular diversity of progenitor cells and their lineages. We identified multiple RGC classes that initiate parallel lineages, converging onto a common class of newborn neuron. Parallel RGC classes and transcriptomic trajectories were repeated across germinal zones and conserved in ferret and human, but not in mouse. Neurons followed parallel differentiation trajectories in the gyrus and sulcus, with different expressions of human cortical malformation genes. Progenitor cell lineage multiplicity is conserved in the folded mammalian cerebral cortex.
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Project description:Evolution of the mammalian brain encompassed a remarkable increase in size of cerebral cortex, including tangential and radial expansion, but the mechanisms underlying these key parameters are still largely unknown. Here, we identified the novel DNA associated protein TRNP1 as a regulator of cerebral cortical expansion in both these dimensions. Gain and loss of function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion, while lower levels promote radial expansion resulting in a potent increase in the generation of intermediate progenitors and outer radial glial cells resulting in folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences also in the cerebral cortex of human fetuses anticipating radial or tangential expansion respectively. Thus, the dynamic regulation of TRNP1 is critical to regulate tangential and radial expansion of the cerebral cortex in mammals. We performed gene expression microarray analysis on embryonic mouse cerebral cortex derived from Trnp1 knockdown and control animals.
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Project description:Differential gene expression of cerebral cortex might be responsible for distinct neurovascular developments between different mouse strains We used Affymetrix microarray to explore the global gene expression patterns of mouse cerebral cortex of different mouse strains at two developmental stages Cerebral cortex from two mouse strains [C57BL/6J(B6) and C3H/J (C3H)] at post-natal day 1 (p1) and post-natal 11 weeks (11 wk) were harvested for microarray experiments
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Project description:Evolution of the mammalian brain encompassed a remarkable increase in size of cerebral cortex, including tangential and radial expansion, but the mechanisms underlying these key parameters are still largely unknown. Here, we identified the novel DNA associated protein TRNP1 as a regulator of cerebral cortical expansion in both these dimensions. Gain and loss of function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion, while lower levels promote radial expansion resulting in a potent increase in the generation of intermediate progenitors and outer radial glial cells resulting in folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences also in the cerebral cortex of human fetuses anticipating radial or tangential expansion respectively. Thus, the dynamic regulation of TRNP1 is critical to regulate tangential and radial expansion of the cerebral cortex in mammals.
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Project description:Differential gene expression of cerebral cortex might be responsible for distinct neurovascular developments between different mouse strains We used Affymetrix microarray to explore the global gene expression patterns of mouse cerebral cortex of different mouse strains at two developmental stages
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Project description:The cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown. In order to uncover genetic networks underlying the development of the human cerebral cortex, we profiled the transcriptome of human fetal cortical domains containing language areas of Broca and Wernicke, as well as associative areas. We thus identified hundreds of genes displaying differential expression between the two areas or between distinct temporal stages. A subset of these genes was further validated by qRTPCR and in situ hybridization, revealing novel patterns of area and layer-specific expression throughout the developing cortex at midgestation, a critical period of cortical patterning. Computational genomic analyses revealed that the proportion of genes located close to evolutionarily accelerated regions was far more abundant among the genes differentially expressed between the two cortical areas examined, but not among those differentially expressed between different stages of development. In silico screening enabled to identify accelerated regions displaying increased turnover of change in transcription factor binding sites, which were enriched among those closer to genes differentially expressed between cortical areas. Overall our work points to the identification of cortical genes that display a unique combination of patterns of evolution and expression, which may constitute an important part of the genetic framework underlying human-specific neural traits and diseases. We determined gene expression patterns in cortical domains that contain areas thought to have undergone significant divergence during primate evolution, including language areas of Broca and Wernicke, as well as association areas of the frontal and parieto-temporal cortex in the right and left sides of human fetal brains at 17 and 19 gestional weeks.
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