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Development 128, 4881-4890 (2001)
© 2001 The Company of Biologists Limited

Essential role of oligodendrocytes in the formation and maintenance of central nervous system nodal regions

Carole Mathis1, Natalia Denisenko-Nehrbass2, Jean-Antoine Girault2 and Emiliana Borrelli1,*

1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
2 INSERM U536, Institut du Fer à Moulin et Collège de France, 75005 Paris, France

*Author for correspondence (e-mail: eb{at}igbmc.u-strasbg.fr)

Accepted August 28, 2001

The membrane of myelinated axons is divided into functionally distinct domains characterized by the enrichment of specific proteins. The mechanisms responsible for this organization have not been fully identified. To further address the role of oligodendrocytes in the functional segmentation of the axolemma in vivo, the distribution of nodal (Na+ channels, ankyrin G), paranodal (paranodin/contactin-associated-protein) and juxtaparanodal (Kv1.1 K+ channels) axonal markers, was studied in the brain of MBP-TK and jimpy mice. In MBP-TK transgenic mice, oligodendrocyte ablation was selectively induced by FIAU treatment before and during the onset of myelination. In jimpy mice, oligodendrocytes degenerate spontaneously within the first postnatal weeks after the onset of myelination. Interestingly, in MBP-TK mice treated for 1-20 days with FIAU, despite the ablation of more than 95% of oligodendrocytes, the protein levels of all tested nodal markers was unaltered. Nevertheless, these proteins failed to cluster in the nodal regions. By contrast, in jimpy mice, despite a diffused localization of paranodin, the formation of nodal clusters of Na+ channels and ankyrin G was observed. Furthermore, K+ channels clusters were transiently visible, but were in direct contact with nodal markers. These results demonstrate that the organization of functional domains in myelinated axons is oligodendrocyte dependent. They also show that the presence of these cells is a requirement for the maintenance of nodal and paranodal regions.

Key words: Oligodendrocyte, MBP-TK, jimpy, Mouse, Ranvier’s node




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