Axon guidance signal ensures neurite growth pace while sensitizing repulsive cues through induction of a dual function facilitator
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA805510 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17982645.fastq.gz | Fastqsanger.gz | |||
| SRR17982646.fastq.gz | Fastqsanger.gz | |||
| SRR17982647.fastq.gz | Fastqsanger.gz | |||
| SRR17982648.fastq.gz | Fastqsanger.gz | |||
| SRR17982649.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: profiling the differential transcripts usage in wild type and Plxnd1 knockout condition of brain Methods: transcriptome analysis by the RNA-seq through the mRNA pull-down Results: We performed RNA-seq analysis from neonatal mouse striatum and found that the repulsive Semaphorin 3E (Sema3E)-Plexin-D1 guidance signaling transcriptionally upregulates Mtss1 in striatonigral projecting neurons of basal ganglia circuitry Conclusions: our findings demonstrate a molecular mechanism in which repulsive guidance cues activate an autoregulatory program enabling growing axons to perform both avoiding repellants and continuing axonal extension in the navigation to their target
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Project description:Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain. Here, we analyzed quantitative changes in the proteome of neurospheres during differentiation. Relative quantification was performed at early time points during differentiation using iTRAQ-based labeling and LC-MS/MS analysis. We identified 6438 proteins, from which 433 were downregulated and 479 were upregulated during differentiation. We show that human neurospheres have a molecular profile that correlates to the fetal brain. During differentiation, upregulated pathways are related to neuronal development and differentiation, cell adhesion and axonal guidance whereas cell proliferation pathways were downregulated. We developed a functional assay to check for neurite outgrowth in neurospheres and confirmed that neurite outgrowth potential is increased after 10 days of differentiation and is enhanced by increasing cyclic AMP levels. The proteins identified here represent a resource to monitor neurosphere differentiation and coupled to the neurite outgrowth assay can be used to functionally explore neurological disorders using human neurospheres as a model.
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Project description:Cell type diversity during neuro-ectodermal (NE) differentiation is achieved through selective activation and silencing of neurodevelopmental genes. Here, we show a key role for the histone deacetylase complex MiDAC during neuronal differentiation of mouse embryonic stem cells (mESCs) into NE. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC mediates the removal of H4K20ac on the promoters and enhancers of pro-neural genes such as the axon guidance ligands Slit3 and Ntn1 while in parallel reducing H3K27ac on promoter-proximal and -distal elements of negative regulators of neurogenesis thereby upregulating and inhibiting gene expression, respectively. Furthermore, neurite outgrowth defects in MiDAC KO neurons can be rescued by restoring Slit3/Robo3-Ntn1/Unc5b signaling. Taken together, our work suggests a crucial role for MiDAC in regulating the secretome of the Slit3/Robo3-Ntn1/Unc5b signaling axes to ensure the proper integrity of neurite development.
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Project description:Cell type diversity during neuro-ectodermal (NE) differentiation is achieved through selective activation and silencing of neurodevelopmental genes. Here, we show a key role for the histone deacetylase complex MiDAC during neuronal differentiation of mouse embryonic stem cells (mESCs) into NE. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC mediates the removal of H4K20ac on the promoters and enhancers of pro-neural genes such as the axon guidance ligands Slit3 and Ntn1 while in parallel reducing H3K27ac on promoter-proximal and -distal elements of negative regulators of neurogenesis thereby upregulating and inhibiting gene expression, respectively. Furthermore, neurite outgrowth defects in MiDAC KO neurons can be rescued by restoring Slit3/Robo3-Ntn1/Unc5b signaling. Taken together, our work suggests a crucial role for MiDAC in regulating the secretome of the Slit3/Robo3-Ntn1/Unc5b signaling axes to ensure the proper integrity of neurite development.
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Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Keywords: Mutant Analysis
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Project description:This SuperSeries is composed of the following subset Series:; GSE9738: Analysis of gene expression during neurite outgrowth and regeneration (430A and 420A 2.0 array); GSE9739: Analysis of gene expression during neurite outgrowth and regeneration (MG-U74A); GSE9740: Analysis of gene expression during neurite outgrowth and regeneration MG-U74B Experiment Overall Design: Refer to individual Series
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Project description:Developmental alteration in brain wiring that would make it more susceptible to later pathological processes has been suggested as a basis for the occurrence of neurodegenerative diseases, but mechanisms have remained elusive. A recent series of magnetic resonance imaging studies have demonstrated that, in Wolfram syndrome, neurodegenerative processes appear during childhood and adolescence on top of a clinically silent global defect in brain development. Here, differentiation of induced pluripotent stem cell lines derived from Wolfram syndrome patients’ cells along the neural lineage has revealed phenotypic and molecular correlates of that global brain defect. A proportion of neural cells displayed aberrant neurite outgrowth associated with alterations in the expression of genes involved in axonal guidance. In contrast, an activation of endoplasmic reticulum stress response genes was absent while it is present in late Wolfram syndrome degenerative processes. These results concur to the broader hypothesis that axon guidance genes may play a role in the susceptibility to neurodegenerative diseases.
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Project description:During the development of the Drosophila central nervous system the process of midline crossing is orchestrated by a number of guidance receptors and ligands. Many key axon guidance molecules have been identified in both invertebrates and vertebrates, but the transcriptional regulation of growth cone guidance remains largely unknown. One open question is whether transcriptional regulation plays a role in midline crossing, or if local translation can account for the necessary fine tuning of protein levels. To investigate this issue, we conducted a genome wide analysis of transcription in Drosophila embryos using wild type and a number of well-characterized Drosophila guidance mutants and transgenics. We also analyzed a publicly available microarray time course of Drosophila embryonic development with an axon guidance focus. Using hopach, a novel clustering method which is well suited to microarray data analysis, we identified groups of genes with similar expression patterns across guidance mutants and transgenics. We then systematically characterized the resulting clusters with respect to their relevance to axon guidance using two complementary controlled vocabularies: the Gene Ontology (GO) and anatomical annotations of the Atlas of Pattern of Gene Expression (APoGE) in situ hybridization database. The analysis indicates that regulation of gene expression does play a role in the process of axon guidance in Drosophila. We also find a strong link between axon guidance and hemocyte migration, a result that agrees with mounting evidence that axon guidance molecules are co-opted in vertebrate vascularization. Cell cyclin activity in the context of axon guidance is also suggested from our array data. RNA and protein patterns of cell cyclin in axon guidance mutants and transgenics support this possible link. This study provides important insights into the regulation of axon guidance in vivo and suggests that transcription does play a role in control of axon guidance. Experiment Overall Design: Several mutants and transgenics were analyzed, totalizing 17 distinct conditions. Individual descriptions are included in each microarray. For each condition there are 3 or 4 replicates. The file's name indicates the replicates, e.g., comm.a reflects the replicate a of mutant commissureless. The experiment design covers a range of mutants and transgenics of key axon guidance mutans, in different dosages. The protocol was the standard Affymetrix protocol.
2008-06-15 | E-GEOD-6515 | biostudies-arrayexpress
Project description:This study investigates the phenomenon of postnatal plasticity within the enteric nervous system (ENS), specifically investigating the reinnervation potential of post-mitotic enteric neurons. Employing BAF53b-Cre for selective tracing, the reinnervation capabilities of postnatal enteric neurons in multiple model systems are shown. Denervated enteric neurons exhibit the ability to regenerate neurites in vitro, with neurite complexity and direction notably influenced by contact with enteric glial cells (EGCs). In vivo nerve fibers from transplanted enteric neurons exclusively interface with EGCs. Resident EGCs are sustained after Cre dependent ablation of enteric neurons and govern the architecture of the ENS by reinnervating enteric neurons. Transplantation experiments underscore the swift reintegration and reinnervation potential of post-mitotic neurons, leading to restored muscle function within two weeks. Optogenetic investigations further delineate time-dependent functional recovery via transplantation of isolated enteric ganglia. These revelations demonstrate the structural and functional reinnervation capacity of post-mitotic enteric neurons, underscored by EGC guidance.
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2008-06-16 | E-GEOD-9738 | biostudies-arrayexpress