G.P.195: BMP signaling controls satellite cell dependent postnatal muscle growth

Abstract

Postnatal/juvenil muscle growth is achieved by both an increase in myofiber size and the addition of further myonuclei, whereas myofiber number does not increase further. Satellite cells are the resident muscle stem cells which proliferate in growing muscle to supply new myonuclei. Little is known of how satellite cell function is controlled during the postnatal/juvenil growth phase to permit correct muscle mass development and the generation of the adult satellite cell pool. We previously have shown that signaling by Bone morphogenetic proteins (BMP) regulates embryonic myogenesis by determining the entry of embryonic muscle precursors into differentiation. Here we demonstrate that this pathway also defines postnatal/juvenil muscle growth. We found that juvenile satellite cells express elements of the BMP signaling cascade such as BMP ligands, BMP receptor, and the intracellular BMP responsive element P-Smad1/5/8, showing that BMP signaling is active in these cells. Abrogating BMP signaling targeted to satellite cells in juvenile Rosa26-Lox-Stop-Lox-Smad6-IRES-GFP:Pax7CreERT2/+ mice decreased the pool of satellite cells and muscle fibres contained less myonuclei and were smaller than those from control mice. We show that blockade of BMP signaling decreased satellite cell proliferation and diminished the myonuclear recruitment during myofiber growth as the underlying cellular mechanism, and this severely retarded muscle growth. In addition, failure of satellite cell proliferation strongly reduced the final satellite cell reservoir in mature muscle. In conclusion, these results show that correct BMP signaling in satellite cells is required for satellite cell dependent myofiber growth and for the generation of the adult satellite cell pool. In future it will be of large interest to determine whether the BMP signaling pathway is altered in childhood neuromuscular disorders and whether this inflicts satellite cell dependent muscle growth.