Axoglial Adhesion by Cadm4 Regulates CNS Myelination
| Autor: | Yael Eshed-Eisenbach, Neev Golan, Nimrod Elazar, Nicole Schaeren-Wiemers, Bharath Vijayaragavan, Elior Peles, Anya Vainshtein |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Central Nervous System
Male 0301 basic medicine Genetically modified mouse Transgene Intermediate Filaments Mice Transgenic Article Mice 03 medical and health sciences Myelin 0302 clinical medicine 2' 3'-Cyclic Nucleotide 3'-Phosphodiesterase Ganglia Spinal Cell Adhesion medicine Extracellular Animals Rats Wistar Receptor Cells Cultured Myelin Sheath Neurons Oligodendrocyte Precursor Cells Cell adhesion molecule Chemistry General Neuroscience Adhesion Axons Coculture Techniques Cell biology Mice Inbred C57BL Oligodendroglia 030104 developmental biology medicine.anatomical_structure Animals Newborn nervous system Female Cell Adhesion Molecules 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Neuron. 101:224-231.e5 |
| ISSN: | 0896-6273 |
| Popis: | The initiation of axoglial contact is considered a prerequisite for myelination, yet the role cell adhesion molecules (CAMs) play in mediating such interactions remains unclear. To examine the function of axoglial CAMs, we tested whether enhanced CAM-mediated adhesion between OLs and neurons could affect myelination. Here we show that increased expression of a membrane-bound extracellular domain of Cadm4 (Cadm4dCT) in cultured oligodendrocytes results in the production of numerous axoglial contact sites that fail to elongate and generate mature myelin. Transgenic mice expressing Cadm4dCT were hypomyelinated and exhibit multiple myelin abnormalities, including myelination of neuronal somata. These abnormalities depend on specific neuron-glial interaction as they were not observed when these OLs were cultured alone, on nanofibers, or on neurons isolated from mice lacking the axonal receptors of Cadm4. Our results demonstrate that tightly regulated axon-glia adhesion is essential for proper myelin targeting and subsequent membrane wrapping and lateral extension. |
| Databáze: | OpenAIRE |
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