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Abstract
Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double homeobox 4 (DUX4-FL) retrogene in skeletal muscle. However, even in cases of severe FSHD the presence of DUX4 is barely detectable. In this issue of the JCI, Bosnakovski et al. used an inducible, muscle-specific human DUX4 to reproduce the low-level, sporadic DUX4 expression of human FSHD muscle as well the myopathology seen in human FSHD disease. Notably, dysregulated fibroadipogenic progenitors accumulated in affected muscles, thus providing a mechanism for the replacement of muscle by fibrosis and fat.
Authors
Carlo Serra, Kathryn R. Wagner
Figure 1
FAPs’ potential contribution to FSHD myopathy.
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Upon acute muscle injury, normal muscle (center) shows necrosis of the damaged fibers and then the formation of new fibers by the fusion of the resident MuSCs (left). In this context, FAPs proliferate to assist this process and subsequently return to the basal level. Conversely, the continuous cycles of muscle necrosis and regeneration, as in FSHD, result in the excessive deposition of FAPs, a change that helps to explain the massive accumulation of fibrosis and intramuscular fat in the dystrophic muscle (right).
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ISSN: 0021-9738 (print), 1558-8238 (online)