Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation.
Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation.
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在产后发育和加剧期间，ephrin-A3在产后发育和加重过程中促进和维持较慢的肌肉纤维身份。
DOI：
10.1083/jcb.201502036
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发表时间：
2015-12-07
期刊：
影响因子：
--
通讯作者：
Cornelison DD
中科院分区：
文献类型：
--
作者：
Stark DA;Coffey NJ;Pancoast HR;Arnold LL;Walker JP;Vallée J;Robitaille R;Garcia ML;Cornelison DD
During neuromuscular junction maturation and repair, ephrin-A3 is expressed by all slow (Type I) fibers and only by slow fibers, and inhibits their innervation by fast motor axons via repulsive interactions with the ephrin-A3 receptor EphA8. 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.
