Nerve-dependent modulation of acetylcholine receptor epsilon-subunit gene expression.
The relative abundance of mRNAs encoding the gamma- and epsilon-subunits of acetylcholine receptor changes in opposite directions during mouse development. Both gamma- and epsilon-mRNAs are expressed early in muscle development in vivo, and in aneural embryonic muscle and myogenic cell lines in vitro, though gamma-mRNA is at least 20-fold more abundant than epsilon-mRNA in these circumstances. While during normal development, gamma-mRNA decreases to an undetectable level by postnatal day 12, epsilon-mRNA first increases 10-fold between day 2 and day 12-15, then decreases to the level characteristic of adult muscle. We have found that the transition form gamma- to epsilon-mRNA is influenced by the levels of thyroid hormones. Indeed, high and low levels of thyroid hormones, respectively, accelerated and delayed the switch between gamma- and epsilon-mRNAs. Neither the dramatic postnatal rise in epsilon-mRNA nor its sensitivity to thyroid hormones was observed in denervated newborn animals. By contrast, denervation was without effect on epsilon-mRNA expression in adult muscle. These results suggest that, although not required for the initial activation of the epsilon-gene nor its maintenance in adult muscle, the nerve plays a major role in the perinatal regulation of epsilon-gene transcription.
Martinou
J C
JC
Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110.
Merlie
J P
JP
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D006980:Hyperthyroidism / Q000503:physiopathology; D007037:Hypothyroidism / Q000503:physiopathology; D046911:Macromolecular Substances; D051379:Mice; D008813:Mice, Inbred ICR; D009121:Muscle Denervation; D024510:Muscle Development; D009132:Muscles / Q000502:physiology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011950:Receptors, Cholinergic / Q000235:genetics*; D013974:Thyroxine / Q000097:blood; D014158:Transcription, Genetic
D046911:Macromolecular Substances; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D013974:Thyroxine