title: Dystroglycan promotes filopodial formation and process branching in differentiating oligodendroglia.
abstract: During central nervous system (CNS) development, individual oligodendrocytes myelinate multiple axons, thus requiring the outgrowth and extensive branching of oligodendroglial processes. Laminin (Lm)-deficient mice have a lower percentage of myelinated axons, which may indicate a defect in the ability to properly extend and branch processes. It remains unclear, however, to what extent extracellular matrix (ECM) receptors contribute to oligodendroglial process remodeling itself. In the current study, we report that the ECM receptor dystroglycan is necessary for Lm enhancement of filopodial formation, process outgrowth, and process branching in differentiating oligodendroglia. During early oligodendroglial differentiation, the disruption of dystroglycan-Lm interactions, via blocking antibodies or dystroglycan small interfering RNA (siRNA), resulted in decreased filopodial number and length, decreased process length, and decreased numbers of primary and secondary processes. Later in oligodendrocyte differentiation, dystroglycan-deficient cells developed fewer branches, thus producing less complex networks of processes as determined by Sholl analysis. In newly differentiating oligodendroglia, dystroglycan was localized in filopodial tips, whereas, in more mature oligodendrocytes, dystroglycan was enriched in focal adhesion kinase (FAK)-positive focal adhesion structures. These results suggest that dystroglycan-Lm interactions influence oligodendroglial process dynamics and therefore may regulate the myelination capacity of individual oligodendroglia.
authors: Department of Pharmacology, Stony Brook University, Stony Brook, NY, USA.
authors: Christopher
authors: C
authors: Eyermann
authors: Kevin
authors: K
authors: Czaplinski
authors: Holly
authors: H
authors: Colognato
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D049030:Dystroglycans / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018709:Statistics, Nonparametric; D013234:Stem Cells; D013997:Time Factors; D014162:Transfection
chemical_list: D000199:Actins; D000906:Antibodies; D007797:Laminin; D034741:RNA, Small Interfering; D049030:Dystroglycans; D049452:Green Fluorescent Proteins; D016899:Interferon-beta; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse; C571339:Cnp protein, rat