Peripheral axons of Wlds mice, which regenerate after a delay of several weeks, do so readily when transcription is inhibited in the distal stump.

We have raised the hypothesis that differentiated Schwann cells repress regrowth of axons but become permissive upon dedifferentiation. WId(S) mouse is a strain in which severed peripheral nerves do not degenerate for several weeks, and axonal regeneration does not occur either [5,11]. In this strain, we studied the role of resident cells upon axonal regeneration by inhibiting transcription. Regeneration was assessed with the pinch test, electron microscopy and Dil (a fluorescent lipid soluble dye). After a crush, WId(S) axons did not regenerate but they did so when the crush was made through a nerve segment treated with actinomycin D (ActD), an inhibitor of transcription. In contrast, when the crush was made distal to the treated segment no regeneration ensued. Our results support the notion that normal resident cells of peripheral nerves repress axonal growth.