Novel Molecular Mechanisms of Neuronal and Vascular Protection in Experimental Glaucoma

Paranodal axoglial junctions are essential for the segregation of myelinated axonsinto distinct domains and efficient conduction of action potentials. Here, we show thatnetrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNSmyelin. We then address whether netrin-1 signaling influences paranodal adhesionbetween oligodendrocytes and axons. In the absence of netrin-1 or DCC function,oligodendroglial paranodes initially develop and mature normally but later becomedisorganized. Lack of DCC or netrin-1 resulted in detachment of paranodal loops fromthe axonal surface and the disappearance of transverse bands. Furthermore, the domainorganization of myelin is compromised in the absence of netrin-1 signaling: K channelsinappropriately invade the paranodal region, and the normally restricted paranodaldistribution of Caspr expands longitudinally along the axon. Our findings identify anessential role for netrin-1 and DCC regulating the maintenance of axoglial junctions.