Genome-wide analysis of rats' mRNA profile after knocking down PIWIL1 in embryonic cultured neurons.
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE48236 | GEO | 2016/06/22
SECONDARY ACCESSION(S): PRJNA209323
REPOSITORIES: GEO
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Project description:We have demonstrated that PIWIL1 can regulate neuronal radial migration during corticogenesis. In order to explore the mechanism, we carried out high-throughtput sequencing (mRNA profile) to define downstream target of PIWIL during the process of neuronal migration. And we found the expression level of several microtubule-associated proteins decreased after downregulation of PIWIL1. Therefore, PIWIL1 plays an important role in neuronal migration by regulating the expression microtubule-associated proteins (such as Map1B, Map2, Tau) . Examine mRNA profile in two groups of primary cultured neurons with electroporation of control or RNAi plasmid.
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2023-07-04 | PXD042855 | Pride
Project description:The cerebral cortex is a highly organized structure whose development depends on different progenitor cell types. These give rise to post-mitotic neurons that migrate across the developing cortical wall to their final positions in the cortical plate. Apical radial glia cells (aRGs) are the main progenitor type in early corticogenesis, responsible for the production of other progenitors, and regulating the final neuronal output. Abnormal behavior of aRG can severely impact corticogenesis resulting in cortical malformations. Mutations in the microtubule associated protein Eml1 lead to severe subcortical heterotopia, characterized by the presence of aberrantly located neurons beneath the normotopic cortex. Mutations in EML1/Eml1 have been reported in three families presenting severe atypical heterotopia, as well as in the Heterotopic cortex ‘HeCo’ spontaneous mouse mutant. In the latter, ectopically cycling aRGs were found cycling outside their normal proliferative ventricular zone (VZ) from early stages of corticogenesis (Croquelois et al., 2009, Kielar et al., 2014, Shaheen et al., 2017). Ectopic aRGs are likely to be responsible for the formation of the heterotopia. It is thus crucial to understand the role of Eml1 in aRGs to elucidate the physiological and pathological mechanisms causing aRGs to leave the VZ. The role of Eml1 in aRGs remains vastly unexplored. We have thus performed mass spectrometry with embryonic cortex lysates (E13.5) to shed light on the intracellular pathways and molecular mechanisms in which Eml1 could be involved. This data combined with other cell biology and biochemistry approaches will contribute to understand the role of this heterotopia protein at early stages of development.
2019-06-20 | PXD012714 | Pride
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.
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Project description:Bergmann glia (BG) are important in the inward type of radial migration of cerebellar granule neurons (CGNs). However, details regarding the functions of Cdc42 and Rac in BG for radial migration of CGN are unknown. To examine the roles of Cdc42 and Rac in BG during cerebellar corticogenesis, mice with a single deletion of Cdc42 or Rac1 and those with double deletions of Cdc42 and Rac1 under control of the glial fibrillary acidic protein (GFAP) promoter: GFAP-Cre;Cdc42flox/flox (Cdc42-KO), GFAP–Cre;Rac1flox/flox (Rac1-KO), and GFAP-Cre;Cdc42 flox/flox;Rac1flox/flox (Cdc42/Rac1-DKO) mice, were generated. Both Cdc42-KO and Rac1-KO mice, but more obviously Cdc42-KO mice, had disturbed alignment of BG in the Purkinje cell layer (PCL). We found that Cdc42-KO, but not Rac1-KO, induced impaired radial migration of CGNs in the late phase of radial migration, leading to retention of CGNs in the inferior half of the molecular layer (ML). Cdc42-KO, but not Rac1-KO, mice also showed aberrantly aligned Purkinje cells (PCs). These phenotypes were exacerbated in Cdc42/Rac1-DKO mice. Alignment of BG radial fibers in the ML and BG endfeet at the pial surface of the cerebellum evaluated by GFAP staining was disturbed and weak in Cdc42/Rac1-DKO mice, respectively. Our data indicate that that Cdc42 and Rac, but predominantly Cdc42, in BG play important roles during the late phase of radial migration of CGNs. We also report here that Cdc42 is involved in gliophilic migration of CGNs, in contrast to Rac, which is more closely connected to regulating neurophilic migration.
2018-01-01 | GSE106142 | GEO
Project description:Bergmann glia (BG) are important in the inward type of radial migration of cerebellar granule neurons (CGNs). However, details regarding the functions of Cdc42 and Rac in BG for radial migration of CGN are unknown. To examine the roles of Cdc42 and Rac in BG during cerebellar corticogenesis, mice with a single deletion of Cdc42 or Rac1 and those with double deletions of Cdc42 and Rac1 under control of the glial fibrillary acidic protein (GFAP) promoter: GFAP-Cre;Cdc42flox/flox (Cdc42-KO), GFAP–Cre;Rac1flox/flox (Rac1-KO), and GFAP-Cre;Cdc42 flox/flox;Rac1flox/flox (Cdc42/Rac1-DKO) mice, were generated. Both Cdc42-KO and Rac1-KO mice, but more obviously Cdc42-KO mice, had disturbed alignment of BG in the Purkinje cell layer (PCL). We found that Cdc42-KO, but not Rac1-KO, induced impaired radial migration of CGNs in the late phase of radial migration, leading to retention of CGNs in the inferior half of the molecular layer (ML). Cdc42-KO, but not Rac1-KO, mice also showed aberrantly aligned Purkinje cells (PCs). These phenotypes were exacerbated in Cdc42/Rac1-DKO mice. Alignment of BG radial fibers in the ML and BG endfeet at the pial surface of the cerebellum evaluated by GFAP staining was disturbed and weak in Cdc42/Rac1-DKO mice, respectively. Our data indicate that that Cdc42 and Rac, but predominantly Cdc42, in BG play important roles during the late phase of radial migration of CGNs. We also report here that Cdc42 is involved in gliophilic migration of CGNs, in contrast to Rac, which is more closely connected to regulating neurophilic migration.
2018-01-01 | GSE106141 | GEO
Project description:Loss of function of dystonin cytoskeletal linker proteins causes neurodegeneration in the sensory ataxia, dystonia musculorum (dt). While much investigation has focused on understanding dt pathology, divergent functions of dystonin isoforms are still unknown. Here, we highlight a novel function of the dystonin-a2 isoform in mediating microtubule (MT) stability, golgi organization and flux through the secretory pathway. Using dystonin-null mice combined with isoform-specific loss of function analysis, we find dystonin-a2 is bound to MAP1B in the area surrounding the centrosome, where it maintains MT acetylation. In dt, the absence of the MAP1B-dystonin-A2 interaction results in a loss of MAP1B perinuclear localization, leading to MT deacetylation and instability. Deacetylated MTs lead to golgi fragmentation and prevent anterograde trafficking of motor proteins. Maintenance of MT acetylation through TSA administration or MAP1B overexperssion in vitro, mitigates the observed defect. These aberrations are apparent in pre-phenotype dorsal root ganglia (DRG) and primary sensory neurons, suggesting they are causal in the dt disorder.
2012-02-23 | GSE30960 | GEO
Project description:Loss of function of dystonin cytoskeletal linker proteins causes neurodegeneration in the sensory ataxia, dystonia musculorum (dt). While much investigation has focused on understanding dt pathology, divergent functions of dystonin isoforms are still unknown. Here, we highlight a novel function of the dystonin-a2 isoform in mediating microtubule (MT) stability, golgi organization and flux through the secretory pathway. Using dystonin-null mice combined with isoform-specific loss of function analysis, we find dystonin-a2 is bound to MAP1B in the area surrounding the centrosome, where it maintains MT acetylation. In dt, the absence of the MAP1B-dystonin-A2 interaction results in a loss of MAP1B perinuclear localization, leading to MT deacetylation and instability. Deacetylated MTs lead to golgi fragmentation and prevent anterograde trafficking of motor proteins. Maintenance of MT acetylation through TSA administration or MAP1B overexperssion in vitro, mitigates the observed defect. These aberrations are apparent in pre-phenotype dorsal root ganglia (DRG) and primary sensory neurons, suggesting they are causal in the dt disorder. P4 dorsal root ganglia (DRG) tissue from 3 WT and 3 dt27J animals from 2 separate litters was subjected to RNA extraction and analyzed.
2012-02-23 | E-GEOD-30960 | biostudies-arrayexpress
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2010-06-23 | E-GEOD-22513 | biostudies-arrayexpress
Project description:Tissue-wide Mechanisms Overrule Cell-intrinsic Gene Function in Radial Neuronal Migration
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