DIFFERENTIAL EXPRESSION PATTERNS OF 5 ACETYLCHOLINE-RECEPTOR SUBUNIT GENES IN RAT MUSCLE DURING DEVELOPMENT

The spatial and temporal expression patterns of five genes which encod e the alpha-, beta-, gamma-, delta- and epsilon-subunits of the nicoti nic acetylcholine receptor in skeletal muscle were followed during dev elopment in the rat by in situ hybridization analysis. Three major dev elopmental phases, characterized by specific expression patterns, coul d be distinguished. (i) During myogenic differentiation alpha-, beta-, gamma- and delta-subunit genes are activated and transcripts are expr essed in muscle precursor cells at embryonic day 12 (E12) and during s ubsequent cell fusion. (ii) Following innervation of myotubes at simil ar to E15-E17 the mRNA of the alpha-, beta-, gamma- and delta-subunit genes accumulate in synaptic and decrease in extrasynaptic fibre regio ns during early synaptogenesis. The mRNA of the epsilon-subunit gene b ecomes detectable first in subsynaptic nuclei 2-3 days after innervati on has occurred. (iii) During postnatal development alpha-, beta- and delta- subunit transcript levels are reduced predominantly in extrasyn aptic fibre segments and show significant differences in distribution depending on the muscle subtype whereas the gamma-subunit mRNA disappe ars completely within the first postnatal week in all muscles. In cont rast, the epsilon-subunit gene is transcribed only in subsynaptic myon uclei throughout development and in the adult muscle.