Studies on the control of myelinogenesis. IV. Neuronal induction of Schwann cell myelin-specific protein synthesis during nerve fiber regeneration.

The temporal sequence of axon-Schwann cell interaction during regeneration is examined in cat tibial nerves surgically denervated for 8 weeks and, subsequently, coated to a freshly severed peroneal nerve for 3 weeks. Prior to association with regenerating axons, Schwann cells resident in denervated and reinnervated stumps failed to synthesize proteins co-migrant with P0, P1, and P2 myelin proteins in contrast to normal nerves. Axonal association with Schwann cells stimulated synthesis of amino acid-labeled proteins co-migrating with myelin-specific proteins prior to elaboration of myelin lamellae. Radioactivity from these peaks was precipitated by antibodies raised against myelin-specific proteins. The synthesis of P1 and P2 proteins was evident before P0 synthesis in reinnervated stumps. Immunocytochemical staining with antibody to P0, P1, P2, and myelin-associated glycoprotein (MAG) appeared only after myelin lamellae had been formed. These data suggest that Schwann cells: (a) synthesize proteins co-migrant with P1, P2, P0, and MAG in normal cat nerves; (b) cease detectable manufacture of these proteins after axonal loss; (c) regain their capacity to synthesize these proteins upon re-establishment of axonal association; and (d) during regeneration, express the synthesis of P1 and P2 before that of P0.