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 that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through P2 receptors on SCs and intracellular signaling pathways involving Ca2+, Ca2+/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3',5'-monophosphate response element binding protein, and expression of c-fos and Krox-24. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals.