The development of the nervous system depends on dynamic processes that require intense, spatially and temporally regulated cross talk between neurons and their surrounding glial cells. In particular, during both development and nerve fiber repair, motor and sensory axons grow and differentiate in close association with Schwann cells (SCs) that proliferate and migrate along the nerve fibers and drive growth cones to their specific targets. The factors responsible for the interaction between axons and SCs have been only in part identified. Neurotransmitters and their receptors are early expressed during nervous system development suggesting their involvement also in the modulation of axon-glia interaction. The study of the modulation of SC proliferation and differentiation appears relevant to identify new molecules that may play strategic roles in the treatment of nerve regeneration and of acquired peripheral neuropathies.
Recently we demonstrated that Acetylcholine (ACh) via M2 muscarinic receptor activation, inhibited SC proliferation and enhanced differentiation. Our data suggest that M2 receptor may promote SC progression into a differentiated myelinating phenotype, also contributing to the compact myelin organization. Furthermore, it has also been demonstrated the existence of an axo-glial signaling pathway between axonal Neurexins and Neuroligin 3 expressed on oligodendrocytes (OL) and that this contact may contribute to myelinogenesis, to the maintenance of established myelination and to differentiation state of the OL.
In order to better characterize the signals involved in myelinating processes, in particular in peripheral nervous system, we propose to investigate the role of ACh and Neurolighins in regulating peripheral myelination using different in vitro models
