Paranodal axoglial junctions are essential for the segregation of myelinated axons into distinct domains and efficient conduction of action potentials. Here, we show that netrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNS myelin. We then address whether netrin-1 signaling influences paranodal adhesion between oligodendrocytes and axons. In the absence of netrin-1 or DCC function, oligodendroglial paranodes initially develop and mature normally but later become disorganized. Lack of DCC or netrin-1 resulted in detachment of paranodal loops from the axonal surface and the disappearance of transverse bands. Furthermore, the domain organization of myelin is compromised in the absence of netrin-1 signaling: K+ channels inappropriately invade the paranodal region, and the normally restricted paranodal distribution of Caspr expands longitudinally along the axon. Our findings identify an essential role for netrin-1 and DCC regulating the maintenance of axoglial junctions.
Pubmed ID: 18945908 RIS Download
Mesh terms: Animals | Animals, Newborn | Axons | Cell Adhesion Molecules | Cell Adhesion Molecules, Neuronal | Cerebellum | Gap Junctions | Gene Expression Regulation | Male | Mice | Mice, Knockout | Microscopy, Electron, Transmission | Myelin Basic Protein | Nerve Growth Factors | Oligodendroglia | Organ Culture Techniques | Rats | Rats, Sprague-Dawley | Receptors, Cell Surface | Retina | Stem Cell Transplantation | Stem Cells | Time Factors | Tumor Suppressor Proteins
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