Tissue-wide Mechanisms Overrule Cell-intrinsic Gene Function in Radial Neuronal Migration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA825516 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18713900.fastq.gz | Fastqsanger.gz | |||
| SRR18714000.fastq.gz | Fastqsanger.gz | |||
| SRR18714100.fastq.gz | Fastqsanger.gz | |||
| SRR18713901.fastq.gz | Fastqsanger.gz | |||
| SRR18714001.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 259 |
Similar Datasets
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.
2022-06-30 | GSE200604 | GEO
Project description:We investigated two microenvironmental factors, tumor-intrinsic hypoxia, and tumor-secreted factors (secretome) as triggers of collective migration using a three-dimensional (3D) discrete-sized microtumor models that recapitulate hallmarks of Ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition. These two factors induced two distinct modes of collective migration: directional and radial migration in the 3D microtumors generated from the same breast cancer cell line model, T47D. Without external stimulus, large (>500µm) T47D microtumors exhibited tumor-intrinsic hypoxia and directional collective migration while small (<150 µm), non-hypoxic microtumors exhibited radial collective migration only when exposed to secretome of large microtumors. To investigate the differences in the underlying mechanism present between hypoxia- and secretome-induced directional versus radial migration modes, we performed differential gene expression analysis of hypoxia- and secretome-induced migratory microtumors vs. non-hypoxic, non-migratory small microtumors as controls. We used microarrays to detail the global programme of gene expression profiling to study tumor intrinsic hypoxia induced directional migration and secretom induced radial migrartion in large 600µm microtumors with small 150μm microtumors as controls in three dimensional (3D) breast microtumor model
2021-03-26 | GSE166211 | GEO
Project description:When either Panc-1 or MiaPaCa-2 were plated as a discrete clump of cells in the middle of a plate, two morphologically distinct populations could be created. The cells on the periphery of the cell cluster migrated away from the region of high cell density and took on a classical mesenchymal phenotype with spindle like projections and loss of cell to cell adhesion. Cells that remained in the highly populated center showed greater intercellular adhesion and were more rounded in appearance. This model was included to provide information about whether glyco-gene expression changes observed in models of the epithelial to mesenchymal transition also are involved in migration. Radial Migration Assay comparing two populations (Migrating vs. Non Migrating) in two pancreatic cancer cell lines (Panc-1 and MiaPaCa-2)
2010-05-27 | E-GEOD-21566 | biostudies-arrayexpress
Project description:Completion of neuronal migration is critical for brain development. Kif21b is a plus-end directed kinesin motor protein that promotes intracellular transport and controls microtubule dynamics in neurons. Here we report a physiological function of Kif21b during radial migration of projection neurons in the mouse developing cortex. In vivo analysis in mouse and live imaging on cultured slices demonstrate that Kif21b regulates the radial glia-guided locomotion of new-born neurons independently of its motility on microtubules. Unexpectedly we show that Kif21b directly binds and regulates the actin cytoskeleton both in vitro and in vivo in migratory neurons. We establish that Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion. Altogether, our results reveal atypical roles of Kif21b on the actin cytoskeleton during migration of cortical projection neurons
2023-07-04 | PXD042855 | Pride
Project description:During adult neurogenesis, newly formed olfactory bulb (OB) interneurons migrate radially to integrate into specific layers of the OB. Despite the importance of this process, the intracellular mechanisms that regulate radial migration remain poorly understood. Here we find that microRNA (miRNA) let-7 regulates radial migration by modulating autophagy in new-born neurons. Using Argonaute2-immunoprecipitation, we performed global profiling of miRNAs in adult-born OB neurons and identified let-7 as a highly abundant miRNA family. Knockdown of let-7 in migrating neuroblasts prevented radial migration and led to an immature morphology of newly formed interneurons. This phenotype was accompanied by a decrease in autophagic activity. Overexpression of Beclin-1 or TFEB in new-born neurons lacking let-7 resulted in re-activation of autophagy and restored radial migration. Thus, these results reveal a miRNA-dependent link between autophagy and adult neurogenesis with implications for neurodegenerative diseases where these processes are impaired.
2017-03-28 | GSE83903 | GEO
Project description:Loss of BAF complex in developing cortex perturbs radial neuronal migration in a WNT signaling-dependent manner
| PRJNA732078 | ENA
Project description:The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/- and FoxO6-/- mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6 We then show that FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression. Finally, ectopic Plxna4 expression restores radial migration in FoxO6+/- and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.
2016-11-11 | GSE71954 | GEO
Project description:Human brain development is a complex process involving neural proliferation, differentiation, and migration which are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing(RNA-Seq) dataset, we identified synaptotagmin-like 3(SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibited high activity but low expression in both early developmental human cortex and human embryonic stem cell(hESC)-derived neurons. Knockout of SYTL3(SYTL3 -KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promoted neuronal migration. Besides, SYTL3-KO caused an abnormal distribution of deep-layer neurons in brain organoids and reduced presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrated that SYTL3-KO- accelerated neuronal migration was modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identified SYTL3 as a novel regulator of cortical neuronal migration in human and mouse developing brains.
2021-02-07 | E-MTAB-10058 | biostudies-arrayexpress
Project description:Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. Recent evidence suggests that distinct signalling cues act cell-autonomously but differentially at particular steps during the overall migration process. Functional MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. In this project, we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-autonomous and/or community effects, focusing on the Cdk5r1 gene, a neuron-specific activator of Cyclin Dependent Kinase 5 known to play a role, among other functions, in neuronal migration during brain development. This dataset corresponds to a TMT-10plex based proteomics analysis of the effects of full or mosaic KO of Cdk5r1 on the neuronal proteome and aims to provide insights into its distinct cell-autonomous and non-autonomous roles in neuronal migration. This dataset and complementary experimental approaches were integrated using computational modelling to define so far unknown cell-autonomous functions of candidate signalling pathways intersecting with non-cell-autonomous effects to coordinate radial neuron migration.
2024-05-22 | PXD023222 | Pride
Project description:7q11.23 CNV alters ribosomal biogenesis, mTOR and neuronal intrinsic excitability
| PRJNA1088432 | ENA