Synaptic basal lamina contains a signal for synapse-specific transcription

Abstract

Nuclei in the synaptic region of multinucleated skeletal myofibers are transcriptionally distinct, since acetylcholine receptor genes are transcribed at a high rate by these nuclei, but not by nuclei elsewhere in the myofiber. Although this spatially restricted transcription pattern is presumably imposed by the motor nerve, the continuous presence of the nerve is not required, since synapse-specific transcription persists after denervation. These results suggest either that a transcriptional signal persists at synaptic sites after nerve terminals have degenerated, or that a transcriptional pattern in the myofiber, once established, is stable in the absence of a nerve-derived signal. To distinguish between these possibilities, we denervated muscle and damaged the myofibers and specialized cells located near synaptic sites, and then studied transcription of an acetylcholine receptor gene in myofibers that regenerated in their original basal lamina sheaths, but remained denervated. We show that synapse-specific transcription is re-induced in these regenerated myofibers, and we conclude that a signal for synapse-specific transcription is stably maintained in the synaptic basal lamina.