Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons
Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons
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DOI：
10.1242/dev.053348
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发表时间：
2010-10-15
期刊：
影响因子：
4.6
通讯作者：
Sanes, Joshua R.
中科院分区：
文献类型：
--
作者：
Chakkalakal, Joe V.;Nishimune, Hiroshi;Sanes, Joshua R.
哺乳动物四肢和躯干骨骼肌由收缩和分子特性不同的肌纤维组成。它们通常根据其表达的肌球蛋白重链分为四类：I，IIA，IIX和IIB，从最慢到最快。单个的运动轴突支配数十个肌纤维，几乎所有的肌纤维都是相同类型的。解释这种显著特异性的机制，称为运动单位同质性，仍然不完全清楚，部分原因是没有运动神经元类型的标记。在这里，我们表明，在小鼠中，突触囊泡蛋白SV 2A是选择性地定位在运动神经末梢的慢（I型和小IIA型）肌纤维;其近亲，SV 2B和SV 2C，是目前在所有的运动神经末梢。SV 2A在出生时广泛表达;在出生后第一周，快速运动神经元下调其表达。一个可诱导的转基因纳入从Sv 2a基因的调控元件允许选择性标记的慢运动单位，并揭示其组成。肌纤维中转录辅助调节因子PGC 1 α的过度表达，将其转化为缓慢表型，导致SV 2A阳性运动神经末梢的频率增加，表明肌纤维对其神经支配的纤维类型特异性逆行影响。这种逆行影响必须与已知的顺行影响相结合，以了解运动单位如何变得均匀。
Mammalian limb and trunk skeletal muscles are composed of muscle fibers that differ in contractile and molecular properties. They are commonly divided into four categories according to the myosin heavy chain that they express: I, IIA, IIX and IIB, ranging from slowest to fastest. Individual motor axons innervate tens of muscle fibers, nearly all of which are of the same type. The mechanisms accounting for this striking specificity, termed motor unit homogeneity, remain incompletely understood, in part because there have been no markers for motoneuron types. Here we show in mice that the synaptic vesicle protein SV2A is selectively localized in motor nerve terminals on slow ( type I and small type IIA) muscle fibers; its close relatives, SV2B and SV2C, are present in all motor nerve terminals. SV2A is broadly expressed at birth; fast motoneurons downregulate its expression during the first postnatal week. An inducible transgene incorporating regulatory elements from the Sv2a gene permits selective labeling of slow motor units and reveals their composition. Overexpression of the transcriptional co-regulator PGC1 alpha in muscle fibers, which converts them to a slow phenotype, leads to an increased frequency of SV2A-positive motor nerve terminals, indicating a fiber type-specific retrograde influence of muscle fibers on their innervation. This retrograde influence must be integrated with known anterograde influences in order to understand how motor units become homogeneous.