| First Author | Stark DA | Year | 2015 |
| Journal | J Cell Biol | Volume | 211 |
| Issue | 5 | Pages | 1077-91 |
| PubMed ID | 26644518 | Mgi Jnum | J:230727 |
| Mgi Id | MGI:5763684 | Doi | 10.1083/jcb.201502036 |
| Citation | Stark DA, et al. (2015) Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation. J Cell Biol 211(5):1077-91 |
| abstractText | Each adult mammalian skeletal muscle has a unique complement of fast and slow myofibers, reflecting patterns established during development and reinforced via their innervation by fast and slow motor neurons. Existing data support a model of postnatal "matching" whereby predetermined myofiber type identity promotes pruning of inappropriate motor axons, but no molecular mechanism has yet been identified. We present evidence that fiber type-specific repulsive interactions inhibit innervation of slow myofibers by fast motor axons during both postnatal maturation of the neuromuscular junction and myofiber reinnervation after injury. The repulsive guidance ligand ephrin-A3 is expressed only on slow myofibers, whereas its candidate receptor, EphA8, localizes exclusively to fast motor endplates. Adult mice lacking ephrin-A3 have dramatically fewer slow myofibers in fast and mixed muscles, and misexpression of ephrin-A3 on fast myofibers followed by denervation/reinnervation promotes their respecification to a slow phenotype. We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life. |
