Formation of the vertebrate neuromuscular junction.

The sequence of events leading to the formation of the NMJ based on the data presented in this chapter from rat, chick, and Xenopus muscle can be divided into three developmental stages, as shown in Table I. The essential components of the NMJ are acquired early. Acetylcholine is present and can be released from the growing nerve. Acetylcholine receptors are present in the muscle membrane and are functional even at the earliest times. These components of the junction--ACh release and functional ACh receptors--can develop independently of each other; i.e., cell culture studies have shown that nerve cells are capable of releasing ACh before their growing tips have come into contact with the postsynaptic muscle membrane. Conversely, muscle cells grown without nerve synthesize and incorporate in their membranes functional ACh receptors. This situation ensures that functional (table; see text) contacts can occur even at the earliest times. Local accumulation of ACh receptors is also detected at the earliest times of junction formation. Although cell culture studies have demonstrated that receptors can aggregate in the absence of nerve, it would appear that the nerve plays an important role in directing where the highest density of receptors will be localized. Acetylcholinesterase, identified both histochemically and electrophysiologically, occurs at the presumptive NMJ shortly after synaptic transmission and receptor clustering have begun, suggesting that these events may play a role in localizing cholinesterase. Although the studies on rat and chick muscle support this view, development of AChE on Xenopus muscle does not require prior exposure to nerve or muscle activity. The ultrastructural features characteristic of the adult NMJ also do not become apparent until after synaptic transmission and receptor clustering have been seen. However, detection of small regions of specialization could be easily overlooked at the ultrastructural level, particularly if the tissue has not been serially sectioned. The young tissue is more fragile (Gordon et al., 1974) and may be more susceptible to mechanical damage or alterations from the fixation procedures (Kullberg et al., 1977). For these reasons, results pertaining to when the ultrastructural specializations occur are difficult to interpret and must await identification of these structures by other means. A number of other changes occur at the NMJ late in development: (1) ACh receptors become metabolically more stable, (2) there is a conversion in the kinetics of the ACh receptor channel, and (3) junctional folds become apparent. The extent to which these changes occur varies among the different organisms discussed.(ABSTRACT TRUNCATED AT 400 WORDS)