RGD Reference Report - Convergent functional genomics of oligodendrocyte differentiation identifies multiple autoinhibitory signaling circuits. - Rat Genome Database

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Convergent functional genomics of oligodendrocyte differentiation identifies multiple autoinhibitory signaling circuits.

Authors: Gobert, RP  Joubert, L  Curchod, ML  Salvat, C  Foucault, I  Jorand-Lebrun, C  Lamarine, M  Peixoto, H  Vignaud, C  Fremaux, C  Jomotte, T  Francon, B  Alliod, C  Bernasconi, L  Abderrahim, H  Perrin, D  Bombrun, A  Zanoguera, F  Rommel, C  Hooft van Huijsduijnen, R 
Citation: Gobert RP, etal., Mol Cell Biol. 2009 Mar;29(6):1538-53. doi: 10.1128/MCB.01375-08. Epub 2009 Jan 12.
RGD ID: 7775012
Pubmed: PMID:19139271   (View Abstract at PubMed)
PMCID: PMC2648232   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.01375-08   (Journal Full-text)

Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a critical role in oligodendrocyte differentiation, we performed time-dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into process-forming and myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the completely differentiated state, where regulated gene sets overlap maximally. In order to also gain insight into the functional role of genes that are regulated in this process, we silenced 88 of these genes using small interfering RNA and identified multiple repressors of spontaneous differentiation of Oli-neu, most of which were confirmed in rat primary oligodendrocyte precursors cells. Among these repressors were CNP, a well-known myelin constituent, and three phosphatases, each known to negatively control mitogen-activated protein kinase cascades. We show that a novel inhibitor for one of the identified genes, dual-specificity phosphatase DUSP10/MKP5, was also capable of inducing oligodendrocyte differentiation in primary oligodendrocyte precursors. Oligodendrocytic differentiation feedback loops may therefore yield pharmacological targets to treat disease related to dysfunctional myelin deposition.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Dusp10Ratnegative regulation of oligodendrocyte differentiation  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dusp10  (dual specificity phosphatase 10)


Additional Information