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Peripheral nervous system genes expressed in central neurons induce growth on inhibitory substrates.

PloS one | 2012

Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS's enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons.

Pubmed ID: 22701605 RIS Download

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: R01 HD057632
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS059866
  • Agency: NICHD NIH HHS, United States
    Id: HD057632
  • Agency: NINDS NIH HHS, United States
    Id: NS059866

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This is a list of tools and resources that we have found mentioned in this publication.


Brain Gene Expression Map (tool)

RRID:SCR_001517

This database contains gene expression patterns assembled from mouse nervous tissues at 4 time points throughout brain development including embryonic (e) day 11.5, e15.5, postnatal (p) day 7 and adult p42. Using a high throughput in situ hybridization approach we are assembling expression patterns from selected genes and presenting them in a searchable database. The database includes darkfield images obtained using radioactive probes, reference cresyl violet stained sections, the complete nucleotide sequence of the probes used to generate the data and all the information required to allow users to repeat and extend the analyses. The database is directly linked to Pubmed, LocusLink, Unigene and Gene Ontology Consortium housed at the National Center for Biotechnology Information (NCBI) in the National Library of Medicine. These data are provided freely to promote communication and cooperation among research groups throughout the world.

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AmiGO (tool)

RRID:SCR_002143

Web tool to search, sort, analyze, visualize and download data of interest. Along with providing details of the ontologies, gene products and annotations, features a BLAST search, Term Enrichment and GO Slimmer tools, the GO Online SQL Environment and a user help guide.Used at the Gene Ontology (GO) website to access the data provided by the GO Consortium. Developed and maintained by the GO Consortium.

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Primer3 (tool)

RRID:SCR_003139

Tool used to design PCR primers from DNA sequence - often in high-throughput genomics applications. It does everything from mispriming libraries to sequence quality data to the generation of internal oligos.

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Allen Institute for Brain Science (tool)

RRID:SCR_006491

Seattle based independent, nonprofit medical research organization dedicated to accelerating the understanding of how human brain works. Provides free data and tools to researchers and educators and variety of unique online public resources for exploring the nervous system. Integrates gene expression data and neuroanatomy, along with data search and viewing tools, these resources are openly accessible via the Allen Brain Atlas data portal. Provides Allen Mouse Brain, Allen Spinal Cord Atlas, Allen Developing Mouse Brain Atlas, Allen Human Brain Atlas,Allen Mouse Brain Connectivity Atlas, Allen Cell Type Database, The Ivy Glioblastoma Atlas Project (Ivy GAP), The BrainSpan Atlas of the Developing Human Brain.

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RMA Express (tool)

RRID:SCR_008549

RMAExpress is a standalone GUI program for Windows (and Linux) to compute gene expression summary values for Affymetrix Genechip data using the Robust Multichip Average expression summary and to carry out quality assessment using probe-level metrics. It does not require R nor is it dependent on any component of the BioConductor project. If focuses on processing 3'' IVT expression arrays, exon and WT gene arrays. What is RMA? RMA is the Robust Multichip Average. It consists of three steps: a background adjustment, quantile normalization (see the Bolstad et al reference) and finally summarization. Some references (currently published) for the RMA methodology are: Bolstad, B.M., Irizarry R. A., Astrand, M., and Speed, T.P. (2003), A Comparison of Normalization Methods for High Density Oligonucleotide Array Data Based on Bias and Variance. Bioinformatics 19(2):185-193 Supplemental information Rafael. A. Irizarry, Benjamin M. Bolstad, Francois Collin, Leslie M. Cope, Bridget Hobbs and Terence P. Speed (2003), Summaries of Affymetrix GeneChip probe level data Nucleic Acids Research 31(4):e15 Irizarry, RA, Hobbs, B, Collin, F, Beazer-Barclay, YD, Antonellis, KJ, Scherf, U, Speed, TP (2002) Exploration, Normalization, and Summaries of High Density Oligonucleotide Array Probe Level Data. Accepted for publication in Biostatistics. [Abstract, PDF, PS, Complementary Color Figures-PDF, Software] What do I need? You will need the appropriate CDF and CEL files for your dataset. For Exon and WT Gene arrays, the PGF and CLF should be used instead of the CDF file to build a CDFRME file. The process for doing this is explained in the user manual. Some pre-built CDFRME files are also available. CDFRME files HuEx_CDFRME.zip (95.9MB) HuGene_CDFRME.zip (5.5MB) MoEx_CDFRME.zip (79.6MB) MoGene_CDFRME.zip (6.3MB) RaEx_CDFRME.zip (48.4MB) RaGene_CDFRME.zip (5.7MB) Can I use affy/BioConductor instead? Of course. Hypothetically you will get the same results from both places, provided you have consistent settings in affy/BioConductor and RMAExpress. Some people prefer the power and flexibility of R and others like the point and click simplicity of a GUI. RMAExpress caters to the second option. Since RMAExpress outputs the computed expression values to a text file, you may of course load the expression measures into R and use features of Bioconductor for the analysis of your gene expression values. You can of course open the results file in any other application that supports importing plain text files. Will I get the same results as I would using affy/Bioconductor? Yes. The results from RMAExpress should be consistent. What are the machine requirements? A good rule of thumb is the more RAM you have the better. I would recommend at least 1GB, though 512MB will work in most situations. At this point the program has been tested using Windows 2000, Windows XP, Windows Vista and Linux. Most recently I have had a report of over 10,000 arrays processed in a single session. Can I do any quality assessment? Yes, store the residuals when you compute the expression values. Then you may examine chip pseudo-images of the residuals. Note that high positive residuals are colored increasingly read and low negative residuals are colored increasingly blue. To better interpret these images and gain a better feel for what is typical you may visit the PLM Image Gallery where images for a number of different datasets are shown. Access to the NUSE and RLE quality assessment metrics is also provided. How do I download and install it? Click here for the current release Windows version. Use the installer to install the program. The current release version number is 1.0 (released June 29, 2008). A pre-built linux version is not currently available, but you may build it using the source code. You can download pre-release versions from the following table (the release versions will be more stable, the development versions may have features that are incomplete or will be removed or altered before the next release was supported by the PGA U01 HL66583.

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Entrez Gene (tool)

RRID:SCR_002473

Database for genomes that have been completely sequenced, have active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. Includes nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases. All entries follow NCBI's format for data collections. Content of Entrez Gene represents result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. Content is updated as new information becomes available.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Crl:LE (tool)

RRID:RGD_2308852

Rattus norvegicus with name Crl:LE from RGD.

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