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Subtypes of neocortical projection neurons over developmental time

ABSTRACT: Subtypes of neocortical projection neurons over developmental time

PROVIDER: PRJNA477373 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7410550_1.fastq.gz	Fastqsanger.gz
	SRR7410550_2.fastq.gz	Fastqsanger.gz
	SRR7410560_1.fastq.gz	Fastqsanger.gz
	SRR7410560_2.fastq.gz	Fastqsanger.gz
	SRR7410551_1.fastq.gz	Fastqsanger.gz

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Gene expression of subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific chromatin accessibility

Project description:Gene expression of subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific chromatin accessibility

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Specific chromatin accessibility in subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific gene expression

Project description:Specific chromatin accessibility in subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific gene expression

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Subtypes of neocortical projection neurons over developmental time

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-06-21 | GSE116147 | GEO

Gene expression of subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific chromatin accessibility

Project description:Excitatory projection neurons of the neocortex can be classified as occupying the upper layers, layers 2-4, or the deep layers, layers 5 and 6. It is still unclear which transcription factors are required to specify one cell fate versus another and which downstream targets confer specific aspects of neuronal identity over developmental time. To identify transcription factors that specify upper layer versus deep layer fate, we analyzed cell type specific gene expression and differential chromatin accessibility over three defined stages of development. We found that transcription factor expression can distinguish upper layers from deep layers, and cell type specific transcription factor genes have differentially accessible chromatin in their regulatory domains, which tends to be correlated with gene expression.

2019-06-21 | GSE116146 | GEO

Specific chromatin accessibility in subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific gene expression

Project description:Excitatory projection neurons of the neocortex can be classified as occupying the upper layers, layers 2-4, or the deep layers, layers 5 and 6. It is still unclear which transcription factors are required to specify one cell fate versus another and which downstream targets confer specific aspects of neuronal identity over developmental time. To identify transcription factors that specific upper layer versus deep layer fate, we analyzed cell type specific gene expression and differential chromatin accessibility over three defined stages of development. We found that transcription factor expression can distinguish upper layers from deep layers, and cell type-specific transcription factor genes have differentially accessible chromatin in their regulatory domains, which tends to be correlated with gene expression.

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Neocortical projection neurons instruct inhibitory interneuron circuit development in a lineage dependent manner

Project description:Neocortical circuits consist of stereotypical motifs that must self-assemble during development. Recent evidence suggests the subtype identity of both excitatory projection neurons (PNs) and inhibitory interneurons (INs) is important for this process. We knocked out the transcription factor Satb2 in PNs to induce those of the intratelencephalic (IT)-type to adopt a pyramidal tract (PT)-type identity. Loss of IT-type PNs selectively disrupted the lamination and circuit integration of INs derived from the caudal ganglionic eminence (CGE). Strikingly, reprogrammed PNs demonstrated reduced synaptic targeting of CGE-derived INs relative to controls. In control mice, IT-type PNs targeted neighboring CGE INs while PT-type PNs did not in deep layers, confirming this lineage-dependent motif. Finally, single cell RNA-sequencing revealed that major CGE IN subtypes were conserved after loss of IT PNs, but with differential transcription of synaptic proteins and signaling molecules. Thus, IT-type PNs influence CGE-derived INs in a non-cell autonomous manner during cortical development.

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Variation in activity state, axonal projection, and position define the transcriptional identity of individual neocortical projection neurons.

Project description:Single-cell RNA sequencing has generated the first catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of a subset of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1023 cellular responses to sensory manipulation demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type biased choices of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype.

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Variation in activity state, axonal projection, and position define the transcriptional identity of individual neocortical projection neurons.

Project description:Variation in activity state, axonal projection, and position define the transcriptional identity of individual neocortical projection neurons.

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Project description:Intrinsic molecular pathways in the central nervous system dictate neuronal cell fate during development. However, interplay of RNA binding proteins (RBPs) dictating mRNA translation, and their spatiotemporal extracellular regulators in neocortical neural stem cells during neurogenesis are poorly understood. Using an unbiased RNAseq screen of polysomes between early and mid-neurogenesis, we identified functionally related mRNA groups and their isoforms are regulated translationally in prenatal neocortices, including mRNAs encoding RBPs. Here, we show that isoforms of the RBP, Hu antigen D (HuD), regulate the balance of neocortical glutamatergic neurons in an isoform-specific manner during development. HuD3 promoted a Cdp+ intracortically projecting neuronal fate, while HuD4 promoted a Tle4+ subcortically projecting neuronal fate. In early neurogenic radial glia of the neocortex, HuD transcripts were bound and translationally repressed by another RBP, CUG triplet repeat RNA-binding protein 1 (Cugbp1). Cugbp1 knockdown increased the number of Cdp+ intracortically projecting neurons, while having distinct effects on Tle4+ and Ctip2+ subcortically projecting neurons. Neurotrophin-3 promoted HuD3 mRNA translation and Cdp+ fate, which was reversed by Cugbp1. Thus, our findings reveal a novel post-transcriptional molecular pathway in the developing neocortex that regulates the balance of distinct subpopulations of neocortical projection neurons.

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Neocortical projection neurons instruct inhibitory interneuron circuit development in a lineage dependent manner

Project description:Neocortical projection neurons instruct inhibitory interneuron circuit development in a lineage dependent manner

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