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Perspective and significance

Although for many years it has been appreciated that myelinating glial cells and their underlying axons are engaged in a complex dialogue which is crucial for the normal function of both cell types, the identity of the molecules that mediate this interaction remained almost completely unknown. Recent studies by members of the consortium contributed significantly to our current understanding how myelinating glial cells communicate with the axons they ensheath. The studies proposed in this framework will provide important insight on the molecular mechanisms that control myelination and the functional organization of the axon. Uncovering the mechanisms by which myelinating glial cells recognize and ensheath their associated axons is highly significant given the high prevalence of human diseases resulting from demyelination or alteration in myelin, such as multiple sclerosis and a number of inherited neuropathies.

Many developmental mechanisms are recapitulated after injury and pathology in these diseases, and can be exploited to promote regeneration, remyelination and re-establishment of functional axo-glial units. Furthermore, understanding the molecular basis for axo-glial contact is of particular interest as it is becoming increasingly evident that although in many of these disease the first pathological event is the disruption of myelin, secondary changes in the axon, which eventually lead to axonal loss is the main cause of clinical impairment. In summary, the present collaboration is aimed to uncover the molecular mechanisms that govern the Schwann cell-axon engagement, myelination, and the establishment of distinct structural domains, all of which are processes that are crucial for the generation of a fully functional myelinated nerve. Increased knowledge about these mechanisms will prove useful in the design of therapeutical strategies for many neuropathies and demyelinating disorders.