IMPRINTING OF ACETYLCHOLINE-RECEPTOR MESSENGER-RNA ACCUMULATION IN MAMMALIAN NEUROMUSCULAR SYNAPSES

IN mammalian muscle, the subunit composition of the nicotinic acetylcholine receptor (AChR) and the distribution of AChRs along the fibre are developmentally regulated. In fetal muscle, AChRs are distributed over the entire fibre length whereas in adult fibres they are concentrated at the end-plate1. We have used in situ hybridization techniques to measure the development of the synaptic localization of the messenger RNAs (mRNAs) encoding the α-subunit and the Σ-subunit of the rat muscle AChR. The α-subunit is present in both fetal and adult muscle, whereas the Σ-subunit appears postnatally and specifies the mature AChR subtype2-4. The synaptic localization of α-subunit mRNA in adult fibres may arise from the selective down-regulation of constitutively expressed mRNA from extrasynaptic fibre segments. In contrast, Σ-subunit mRNA appears locally at the site of neuromuscular contact and its accumulation at the end-plate is not dependent on the continued presence of the nerve terminal very early during synapse formation. This suggests that Σ-subunit mRNA expression is induced locally via a signal which is restricted to the end-plate region and is dependent on the presence of the nerve only during a short period of early neuromuscular contact. Evidently, several mechanisms operate to confine AChR mRNAs to the adult end-plate region, and the levels of α-subunit and Σ-subunit mRNAs depend on these mechanisms to differing degrees. ö © 1990 Nature Publishing Group.