I have been asked by a student about the coordination of the nuclei within skeletal muscle fibers. Is there transcriptional control between the nuclei of the syncytium?

The basic question being asked here seems to be whether the multiple nuclei in a mature skeletal muscle fiber communicate with one another. The simple answer is, of course, yes. Owing to a long list of molecules that are known to shuttle back and forth between the nucleus and cytoplasm, there are constant reciprocal influences exchanged between the nucleus and cytoplasm in all cells (Cole & Hammell, 1998). As is now well understood from highly publicized animal cloning experiments (e.g., Dolly the sheep; Wilmut et al., 1997), the insertion of a nucleus from an adult cell into the cytoplasm of a fertilized egg from which the host nucleus has been eliminated, allows the information in the adult nucleus to be used to regulate the subsequent development of a complete individual. Thus the cytoplasm in which a nucleus is immersed strongly influences nuclear transcription. In the case of skeletal muscle fibers, where multiple nuclei are immersed in a “common cytoplasm” (the syncytium), nuclear events are naturally coordinately regulated by the syncytium, and individual nuclei coordinately regulate one another through their effects on the cytoplasm. Periodic contraction of the muscle fibers can be expected to “mix” diffusible cytoplasmic factors and maintain a more random distribution.

Recent work has suggested, however, that the skeletal muscle nuclei themselves are not randomly positioned, but rather deployed so that each regulates a surrounding cytoplasmic “domain” (Edgerton & Roy, 1991; Rosser et al., 2002). Because differences have been noted in the sizes of these “myonuclear domains” in response to changes associated with muscle development, growth, and atrophy (Wada et al., 2002), the idea that there are limits to the regulatory interactions between nuclei within the same muscle gaining support. How rigorous are these limits and how do they affect muscle structure and function? Good questions! This remains an area of active investigation that could probably benefit from the efforts of your perceptive and inquisitive student.

Helpful references:

Cole, CN, Hammell, C.M. 1998. Nucleocytoplasmic transport: Driving and directing transport [Review article] Current Biology , 8 :R368-R372.

Edgerton, VR; Roy, RR: 1991: Regulation of skeletal muscle fiber size, shape, and function. J. Biomechanics , 24:123-133.

Rosser, W; Dean, M; Bandman, E: 2002. Myonuclear domain size varies along the lengths of maturing skeletal muscle fibers. Int. J. Dev. Biol.. 46:747-754.

Wada, K-I; Takahashi, H; Katsuta, S.; Soya, H.: 2002. No decrease in myonuclear number after long-term denervation in mature mice. Am J Physiol: Cell Physiol 283: C484-C488.

Wilmut, I. , Schnieke, A. E., McWhir, J., Kind, A. J., and Campbell . K. H. S. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810 - 813.