%0 Journal Article %T M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization. %+ Department of Biology and Biotechnology "Charles Darwin" %+ Center for Research in Neurobiology "Daniel Bovet" %+ Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti %+ Department of Biology %+ Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome] (UNIROMA) %+ Department of Farmaceutical and Biomolecular Sciences %A Uggenti, Carolina %A de Stefano, M Egle %A Costantino, Michele %A Loreti, Simona %A Pisano, Annalinda %A Avallone, Bice %A Talora, Claudio %A Magnaghi, Valerio %A Tata, Ada Maria %Z Contract grant sponsor: Progetti di Ricerca “Sapienza,” Universiy of Roma; contract grant number: C26A122HYC to (A.M.T.). Contract grant sponsor: Association Francaise Contre les Myopathies; contract grant number: 14163/2012 (to V.M.). Contract grant sponsor: ASI (Italian Space Agency) (toM.E.D.S.) %< avec comité de lecture %@ 1932-8451 %J Developmental Neurobiology %I Wiley %V 74 %N 7 %P 676-91 %8 2014-06-30 %D 2014 %R 10.1002/dneu.22161 %M 24403178 %K muscarinic receptors, Schwann cells, acetylcholine, myelin proteins, transcription factors %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine-induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c-jun, Notch-1, and Jagged-1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re-distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild-type mice. Therefore, our data demonstrate that acetylcholine mediates axon-glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization. %G English %2 https://riip.hal.science/pasteur-01053826/document %2 https://riip.hal.science/pasteur-01053826/file/Uggenti_c.pdf %L pasteur-01053826 %U https://riip.hal.science/pasteur-01053826 %~ RIIP %~ RIIP_FCB