Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin production.

Tritiated thymidine has been used as a nuclear marker to trace the origin of Schwann cells, sited in the distal stump of a severed unmyelinated nerve, which are able to elaborate myelin around axons regenerating from an anastomosed proximal stump of a severed myelinated nerve. Two types of cross-anastomosis experiments were performed in young, adult rats: (1) the proximal stump of a myelinated sternohyoid nerve was labeled (5 mCi/kg body weight) selectively over a 4-day period of predetermined maximal thymidine uptake and two days later, after flushing the animal repeatedly with cold thymidine, the unmyelinated cervical sympathetic trunk was transected and its unlabeled distal stump linked to the proximal stump of the labeled sternohyoid nerve; (2) the distal stump of an unmyelinated cervical sympathetic trunk was labeled selectively over a 5-day period of predetermined maximal uptake and two days later, after flushing with cold thymidine, the myelinated sternohyoid nerve was severed and its unlabeled proximal stump linked to the labeled distal stump of the cervical sympathetic trunk. The fate of the labeled cells in each type of anastomosis was determined 3 weeks later by autoradiography and liquid scintillation spectrometry. In the first type, a small amount of label had migrated from proximal stumps but labeled Schwann cells were not found in successfully anastomosed distal stumps. In the second type, labeled Schwann cells were seen in the cervical sympathetic trunk in association with myelinated and non-myelinated axons regenerating from the sternohyoid nerve. These data suggest that the presence or absence of myelin formation by a Schwann cell is controlled by some property of the axon with which it is associated. Putative mechanisms underlying neuronal control of myelinogenesis are discussed.