Response of Schwann cells to action potentials in development

Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes, We report t hat impulse activity in premyelinated axons can inhibit proliferation and d ifferentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through PZ receptors on SCs and intracellular signalin g pathways involving Ca2+, Ca2+/calmodulin kinase, mitogen-activated protei n kinase, cyclic adenosine 3',5'-monophosphate response element binding pro tein, and expression of c-fos and Krox-24. Adenosine triphosphate arrests m aturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through;this mec hanism, functional activity in the developing nervous system could delay te rminal differentiation of SCs until exposure to appropriate axon-derived si gnals.