E-GEOD-35616
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA152545
PROVIDER: E-GEOD-35616 | ExpressionAtlas | 2019-05-14
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-35616-analysis-methods.tsv | Tabular | |||
| E-GEOD-35616-analytics.tsv | Tabular | |||
| E-GEOD-35616-analytics.tsv.rounded | Tabular | |||
| E-GEOD-35616-analytics.tsv.undecorated | Tabular | |||
| E-GEOD-35616-analytics.tsv.undecorated.rounded | Tabular |
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Project description:Interneurons navigate along multiple tangential paths to settle into appropriate cortical layer. They undergo saltatory migration, which is paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. However, it remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes deglutamylation, is a pivotal regulator of pausing of cortical interneurons. Moreover, we show that pausing during migration controls the flow of interneurons invading the cortex by generating heterogeinity in movement at the population level. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also secondarily impairs the generation of age-matched upper layer projection neurons.
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2014-01-01 | E-GEOD-37601 | biostudies-arrayexpress
Project description:We report the expression of selected genes associated with cortical, striatal and olfactory interneurons in hSS-derived Dlxi1/2::eGFP cells before (in hSS) and after migration (in hCS). By fusing hiPSC-derived fusions that were separately patterned to generate either human subpallial spheroids (hSS) or human cortical spheroids (hCS) we are able to model human interneuron migration in vitro. The aim of this experiment is to examine the gene expression of hSS-derived Dlxi1/2::eGFP cells before and after migration.
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Project description:We report the expression of selected genes associated with cortical, striatal and olfactory interneurons in hSS-derived Dlxi1/2::eGFP cells before (in hSS) and after migration (in hCS). By fusing hiPSC-derived fusions that were separately patterned to generate either human subpallial spheroids (hSS) or human cortical spheroids (hCS) we are able to model human interneuron migration in vitro. The aim of this experiment is to examine the gene expression of hSS-derived Dlxi1/2::eGFP cells before and after migration.
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Project description:We report the expression of selected genes associated with cortical, striatal and olfactory interneurons in hSS-derived Dlxi1/2::eGFP cells before (in hSS) and after migration (in hCS). By fusing hiPSC-derived fusions that were separately patterned to generate either human subpallial spheroids (hSS) or human cortical spheroids (hCS) we are able to model human interneuron migration in vitro. The aim of this experiment is to examine the gene expression of hSS-derived Dlxi1/2::eGFP cells before and after migration.
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Project description:The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation is based on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps that are regulated by a large array of signaling pathways. However, based on genetic loss-offunction experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not well understood. Here, we utilized Mosaic Analysis with Double Markers (MADM) technology to either sparsely or globally delete gene function followed by quantitative single cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominates cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically impacts the overall migration phenotype of individual cortical projection neurons. In a broader context our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development (FMCD) in particular, and neurological diseases in general.
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Project description:Malformations of cortical development are the underlying eitiology of many cases of Mental Retardation and Epilepsy. Subtle, below the resolution of current MRI, cortical dysplasias are probably involved in many cases of MR, Epilepsy and Autism for which no diagnosis can currently be made. Therefore, understanding the process of cortical development will be vital in diagnosing and eventual treatment of many patients with these conditions. More specifically, the cortex forms from two major populations of neuroblasts which reach their final destination in the cortex by differerent mechanisms. One is radial migration from ventricular neuroblasts to the cortical plate. These cells are excititory projection neurons and glia. The second pathway is from the ventral ganglionic eminences and tangential migration of the interneuronal population of primarily inhibitory neurons. Much less is known about the control of the latter process, and many of these currently undiagnosed subtle malformations may stem from abnormalities of this tangential migration. This project focuses on the understanding the control of the tangentially migrating inhibitory interneurons. We aim to uncover the transcriptional differences between two distinct neuronal populations, GFP positive cells in the ganglionic emience and GFP positive cells within the cortical plate, in order to understand the genetic control of tangential migration. We will acomplish this aim by targeting two different labeled transcripts againts the affymetrix mouse genome arrays. We hypothesis that there will be distinct differences in mRNA transcription profiles between the ganglionic eminence and cortical plate within developing interneurons. The differences in transcript profiles will be genes that regulate the migration and differentiation of these developing neurons. Transgenic mice have been generated which express green flourscent protien (GFP) based on the activity of the Dlx 5-6 promotor. Dlx 5-6 are highly regulated genes, and are expressed only in developing interneurons with in the embryonic brain. The expression of this gene begins at around E8 within the medial and lateral ganglionic eminence (GE) and then remain present as cells born within these regions migrate out into the developing cortex. Therefore, we can take advantage of these mice by harvesting embryos at a midpoint in their development (E13.5-14.5) and dissect out GFP positive cells from the ganglionic eminence and from the cortical plate. In order to obtain enough cells to extract sufficent mRNA, we have choosen to perform microdisction of the entire GE and entire cortical plate then break up the tissue into single cell suspension and Florescent activated cell sort (FACs) the populations of GFP + and GFP - cells. We then will extract the total RNA from the GFP postive cell populations using a Trizol based method and purify the RNA with a Quiagen column purification method. The purified RNA will then be amplified using the Affymetrix 1 or 2 round T7 based amplification procedure in order to generate the microgram quantities of labelled cRNA. The labelled biotin cRNA will be sent to the microarray consortium for hybridization againt the Affy mouse genome chip. Three embryos will be pooled in order to obtain sufficent RNA and 6 GFP positive GE and cortical plate samples will be used. The six replicates will be obtained from at least 3 different pregnant mice.
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