Molecular mechanisms of bidirectional axon- oligodendrocytes signaling during the initial stages of myelination

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The goal of the study was to investigate the molecular mechanisms of bidirectional axon- oligodendrocytes (OL) signaling during the initial stages of myelination by testing the hypothesis : Mediators of initial axon-to-OL signaling include the neural cell adhesion molecule L1 on OL as well as axonal L1.1. New culture techniques to purify oligodendrocyte precursor cells (OPC) and OL.To search for genes/molecules that control the differentiation of OL, I developed a new cell culture system to get a large number of purified OPC and OL. OPC (NG2+, O1-) cultures were prepared from an embryonic 15〜16 days-old rat cerebrum.2. The expression pattern of L 1 during the development of OL.These studies provide the first evidence that expression of L1 appears in OL, but is absent in OPC. The results suggest that this differential expression pattern of L1 may have functional significance in the initial mechanisms of myelination in brain.3. Relationship between OL and myelination in vitro.The mechanisms controlling myelination at the cellular level are not fully understood. To understand these molecular processes between axon and OL, I developed in vitro myelination system. OL was co-cultured with primary neurons in the presence of astrocytes. These results indicated that L1 is expressed on premeylinated axons and OL, but is down-regulated on fully myelinated axons and OL.The results suggest that this differential expression pattern of L I may have functional significance in the initial mechanisms of myelination in brain.