Increased expression of axogenesis-related genes and mossy fibre length in dentate granule cells from adult HuD overexpressor mice
| Autor: | Federico Bolognani, Joanna Mounce, Daniel C. Tanner, Nora I. Perrone-Bizzozero |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
RNA-binding protein FISH fluorescence in situ hybridization PPF paired-pulse facilitation SPB suprapyramidal bundle Mice 0302 clinical medicine NIH National Institutes of Health Gene expression Gene Regulatory Networks ARE AU-rich element 3' Untranslated Regions Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Expressed sequence tag dentate granule cell General Neuroscience HuD qRT–PCR quantitative reverse transcription–PCR ELAV Proteins gene profiling EST expressed sequence tag GAPDH glyceraldehyde-3-phosphate dehydrogenase GAP-43 growth-associated protein 43 Research Article Transgene T3 3 3′ 5-tri-iodothyronine IPB infrapyramidal bundle αCaMKII α-Ca2+/calmodulin-dependent protein kinase II Mice Transgenic In situ hybridization Biology DGC dentate granule cell S2 lcsh:RC321-571 S4 03 medical and health sciences ARED ARE database 3′-UTR 3′-untranslated region post-transcriptional mechanisms CP choroid plexus T4 thyroxine Animals Gene lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry 030304 developmental biology Dcx doublecortin GO gene ontology KO knockout TTR transthyretin Three prime untranslated region Gene Expression Profiling ISH in situ hybridization IPA ingenuity pathway analysis Molecular biology LCM laser capture microscopy WT wild-type Axons GRE GU-rich element Gene expression profiling SMA spinal muscular atrophy Gene Expression Regulation axonal outgrowth Mtap1b microtubule-associated protein 1b Dentate Gyrus Neurology (clinical) RNA-IP RNA-immunoprecipitation PFA paraformaldehyde DIG digoxigenin 030217 neurology & neurosurgery |
| Zdroj: | ASN NEURO ASN Neuro, Vol 3 (2011) |
| ISSN: | 1759-0914 |
| Popis: | The neuronal RNA-binding protein HuD plays a critical role in the post-transcriptional regulation of short-lived mRNAs during the initial establishment and remodelling of neural connections. We have generated transgenic mice overexpressing this protein (HuD-Tg) in adult DGCs (dentate granule cells) and shown that their mossy fibres contain high levels of GAP-43 (growth-associated protein 43) and exhibit distinct morphological and electrophysiological properties. To investigate the basis for these changes and identify other molecular targets of HuD, DGCs from HuD-Tg and control mice were collected by LCM (laser capture microscopy) and RNAs analysed using DNA microarrays. Results show that 216 known mRNAs transcripts and 63 ESTs (expressed sequence tags) are significantly up-regulated in DGCs from these transgenic mice. Analyses of the 3′-UTRs (3′-untranslated regions) of these transcripts revealed an increased number of HuD-binding sites and the presence of several known instability–conferring sequences. Among these, the mRNA for TTR (transthyretin) shows the highest level of up-regulation, as confirmed by qRT–PCR (quantitative reverse transcription–PCR) and ISH (in situ hybridization). GO (gene ontology) analyses of up-regulated transcripts revealed a large overrepresentation of genes associated with neural development and axogenesis. In correlation with these gene expression changes, we found an increased length of the infrapyramidal mossy fibre bundle in HuD-Tg mice. These results support the notion that HuD stabilizes a number of developmentally regulated mRNAs in DGCs, resulting in increased axonal elongation. |
| Databáze: | OpenAIRE |
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