Covault J, Sanes J R
J Cell Biol. 1986 Mar;102(3):716-30. doi: 10.1083/jcb.102.3.716.
Previous studies of denervated and cultured muscle have shown that the expression of the neural cell adhesion molecule (N-CAM) in muscle is regulated by the muscle's state of innervation and that N-CAM might mediate some developmentally important nerve-muscle interactions. As a first step in learning whether N-CAM might regulate or be regulated by nerve-muscle interactions during normal development, we have used light and electron microscopic immunohistochemical methods to study its distribution in embryonic, perinatal, and adult rat muscle. In embryonic muscle, N-CAM is uniformly present on the surface of myotubes and in intramuscular nerves; N-CAM is also present on myoblasts, both in vivo and in cultures of embryonic muscle. N-CAM is lost from the nerves as myelination proceeds, and from myotubes as they mature. The loss of N-CAM from extrasynaptic portions of the myotube is a complex process, comprising a rapid rearrangement as secondary myotubes form, a phase of decline late in embryogenesis, a transient reappearance perinatally, and a more gradual disappearance during the first two postnatal weeks. Throughout embryonic and perinatal life, N-CAM is present at similar levels in synaptic and extrasynaptic regions of the myotube surface. However, N-CAM becomes concentrated in synaptic regions postnatally: it is present in postsynaptic and perisynaptic areas of the muscle fiber, both on the surface and intracellularly (in T-tubules), but undetectable in portions of muscle fibers distant from synapses. In addition, N-CAM is present on the surfaces of motor nerve terminals and of Schwann cells that cap nerve terminals, but absent from myelinated portions of motor axons and from myelinating Schwann cells. Thus, in the adult, N-CAM is present in synaptic but not extrasynaptic portions of all three cell types that comprise the neuromuscular junction. The times and places at which N-CAM appears are consistent with its playing several distinct roles in myogenesis, synaptogenesis, and synaptic maintenance, including alignment of secondary along primary myotubes, early interactions of axons with myotubes, and adhesion of Schwann cells to nerve terminals.
先前对失神经支配和培养的肌肉的研究表明，肌肉中神经细胞黏附分子（N-CAM）的表达受肌肉的神经支配状态调控，且N-CAM可能介导一些对发育至关重要的神经-肌肉相互作用。作为了解N-CAM在正常发育过程中是否可能调控神经-肌肉相互作用或受其调控的第一步，我们运用光镜和电镜免疫组织化学方法研究了其在胚胎期、围产期和成年大鼠肌肉中的分布。在胚胎肌肉中，N-CAM均匀存在于肌管表面和肌内神经中；在体内和胚胎肌肉培养物中的成肌细胞上也有N-CAM。随着髓鞘形成，N-CAM从神经中消失，随着肌管成熟，N-CAM也从肌管中消失。N-CAM从肌管突触外部分的消失是一个复杂的过程，包括随着次级肌管形成而迅速重排、胚胎发育后期的下降阶段、围产期的短暂重现以及出生后前两周更逐渐的消失。在整个胚胎期和围产期，N-CAM在肌管表面的突触和突触外区域以相似水平存在。然而，出生后N-CAM集中在突触区域：它存在于肌纤维的突触后和突触周围区域，在表面和细胞内（在T小管中）均有，但在远离突触的肌纤维部分检测不到。此外，N-CAM存在于运动神经末梢表面和覆盖神经末梢的施万细胞表面，但在运动轴突的有髓部分和正在髓鞘化的施万细胞中不存在。因此，在成年动物中，N-CAM存在于构成神经肌肉接头的所有三种细胞类型的突触部分而非突触外部分。N-CAM出现的时间和地点与其在肌发生、突触发生和突触维持中发挥的几个不同作用一致，包括次级肌管沿初级肌管排列、轴突与肌管的早期相互作用以及施万细胞与神经末梢的黏附。
