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首页> 外文期刊>Development >Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons.
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Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons.

机译：新型的慢运动神经元标记揭示了肌纤维对其神经支配的逆行影响。

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摘要

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 PGC1alpha 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.
机译：哺乳动物的四肢和躯干骨骼肌由收缩和分子特性不同的肌纤维组成。根据表达的肌球蛋白重链，它们通常分为四类：I，IIA，IIX和IIB，范围从最慢到最快。单个运动轴突支配数十条肌肉纤维，几乎所有的纤维都是同一类型。仍未完全理解造成这种惊人特异性的机制，称为运动单位同质性，部分原因是没有运动神经元类型的标记。在这里，我们在小鼠中显示出突触小泡蛋白SV2A选择性地位于慢速（I型和IIA型）肌纤维上的运动神经末梢。它的近亲SV2B和SV2C存在于所有运动神经末梢。 SV2A在出生时被广泛表达;快速运动神经元在产后第一个星期下调其表达。包含来自Sv2a基因的调控元件的可诱导转基因可以选择性标记慢速运动单位并揭示其组成。转录共调节因子PGC1alpha在肌纤维中的过度表达将其转换为慢表型，导致SV2A阳性运动神经末梢的频率增加，表明肌纤维对它们的神经支配具有特定的纤维类型逆行影响。这种逆行影响必须与已知的顺行影响结合在一起，以了解电机单元如何变得均匀。

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