Axoglial Adhesion by Cadm4 Regulates CNS Myelination

Nimrod Elazar, Anya Vainshtein, Neev Golan, Bharath Vijayaragavan, Nicole Schaeren-Wiemers, Yael Eshed-Eisenbach, Elior Peles

Research output: Contribution to journalArticlepeer-review

Abstract

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 oligoden-drocytes 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.

Original languageEnglish
Pages (from-to)224-231.e5
Number of pages8
JournalNeuron
Volume101
Issue number2
Early online date11 Dec 2018
DOIs
StatePublished - 16 Jan 2019

All Science Journal Classification (ASJC) codes

  • General Neuroscience

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