Myoblast and myotude nuclei display similar patterns of heterogneous acetylcholine receptor subunit mRNA expression

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Abstract
Muscle progenitor cells differentiate to myoblasts, and subsequently myotubes, upon expression of muscle specific genes. We and others have previously shown that myotude nuclei, even in the absence of nerve, express AChR α subunit RNA at varying levels, with a small subset (about ten percent) of the nuclei expressing at high levels. These findings raised two important quwstions:(1) is the observed heterogeneneity a unique property of the α subunits, and (2) when does the heterogeneneity begin? In particular, is it induced only at or afer the time of fusion, or does it exist at the myoblast stage? We hasve, therfore, extended our observations to the γ and δ subunits and we also have examined the distributions of AChR α,γ, and δ subunit RNAs in both myoblasts and myotubes. We used intron and intron-exon probes to detect prespliced trascripts or mature mRNAs in the cells. Because inton-containing transcripts are not transported out of the nuclei, the distributions of these transcripts can indicate their expression patterns among nuclei in the same myotubes. Our results show that both myotubes and myotubes have distribution of the AChR α,γ, and δ subunit RNAs which differ sharply from that of the U1 RNA or Myo D. Thus, the heterogeneous expression of AChR genes is not only an intrinsic property of muscle cell nuclei (in the sense that it does not require the presence of nerves), but it also exists prior to fusion. Our results suggest that muscle nuclei attain individualized capacities for AChR subunit mRNA production early in their development. Conceptual models consistend with individuality imply an additional level of regulation beyond the known diffusible transcriptional factors. © Wiley-Liss, Inc.