Figure 8.

Model for slow muscle fiber specification via ephrin-A3/EphA8 repulsive interactions during postnatal synaptic pruning. We hypothesize that after cell-autonomous slow myofiber specification during embryonic and fetal development, MyHC-I–expressing myofibers begin to express ephrin-A3, leading to preferential elimination of synapses with fast motor axons late in NMJ maturation. In the absence of ephrin-A3, because fast motor axons outnumber slow motor axons in most mixed fiber type muscles, this competitive advantage is lost and the slow myofiber population is largely lost as well because of innervation-dependent fiber type switching to a faster phenotype. It is not yet clear what lineage or local signaling factors induce a subset of terminal Schwann cells to become EphA8^+ve, or when and how they become localized to fast NMJs, although they are present at birth and are restricted to maturing fast NMJs by P14 (Fig. S5). We therefore indicate expression of EphA8 only in the final, steady state. WT, wild type.