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    ABSTRACT: The database of Gene Co-Regulation (dGCR) is a web tool for the analysis of gene relationships based on correlated patterns of gene expression over publicly available transcriptional data. The motivation behind dGCR is that genes whose expression patterns correlate across many experiments tend to be co-regulated and hence share biological function. In addition to revealing functional connections between individual gene pairs, extended sets of co-regulated genes can also be assessed for enrichment of gene ontology classes and interaction pathways. This functionality provides an insight into the biological function of the query gene itself. The dGCR web tool extends the range of expression data curated by existing co-regulation databases and provides additional insights into gene function through the analysis of pathways, gene ontology classes and co-regulation modules.
    Preview · Article · Jan 2015
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    ABSTRACT: During development and after birth neural stem cells in the subventricular zone (SVZ) generate neuroblasts that migrate along the rostral migratory stream (RMS) to populate the olfactory bulb (OB) with neurons. Multiple factors promote neuroblast migration, but the contribution that many of these make to guidance within the intact RMS is not known. In the present study we have characterised in detail how endocannabinoid (eCB), BDNF and FGF receptor (FGFR) signalling regulates motility and guidance, and also determined whether any of these receptors operate in a regionally restricted manner. We used in vivo electroporation in postnatal mice to fluorescently label neuroblasts, and live cell imaging to detail their migratory properties. Cannabinoid receptor antagonists rendered neuroblasts less mobile, and when they did move guidance was lost. Similar results were obtained when eCB synthesis was blocked with diacylglycerol lipase (DAGL) inhibitors, and importantly eCB function is required for directed migration at both ends of the RMS. Likewise, inhibition of BDNF signalling disrupted motility and guidance in a similar manner along the entire RMS. In contrast, altering FGFR signalling inhibits motility and perturbs guidance, but only at the beginning of the stream. Inhibition of FGFR signalling in vivo also reduces the length of the leading process on migratory neuroblasts in a graded manner along the RMS. These results provide evidence for a guidance function for all three of the above receptor systems in the intact RMS, but show that FGFR signalling is unique as it is required in a regionally specific manner. Copyright © 2014. Published by Elsevier Inc.
    No preview · Article · Dec 2014 · Molecular and Cellular Neuroscience
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    ABSTRACT: Glial cells constitute a large proportion of the central nervous system (CNS) and are critical for the correct development and function of the adult CNS. Recent studies have shown that specific subtypes of glia are generated through the proliferation of differentiated glial cells in both the developing invertebrate and vertebrate nervous systems. However, the factors that regulate glial proliferation in specific glial subtypes are poorly understood. To address this we have performed global gene expression analysis of Drosophila post-embryonic CNS tissue enriched in glial cells, through glial specific overexpression of either the FGF or insulin receptor. Analysis of the differentially regulated genes in these tissues shows that the expression of known glial genes is significantly increased in both cases. Conversely, the expression of neuronal genes is significantly decreased. FGF and insulin signalling drive the expression of overlapping sets of genes in glial cells that then activate proliferation. We then used these data to identify novel transcription factors that are expressed in glia in the brain. We show that two of the transcription factors identified in the glial enriched gene expression profiles, foxO and tramtrack69, have novel roles in regulating the proliferation of cortex and perineural glia. These studies provide new insight into the genes and molecular pathways that regulate the proliferation of specific glial subtypes in the Drosophila post-embryonic brain.
    Full-text · Article · Sep 2014 · Gene Expression Patterns
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