Development of the vertebrate neuromuscular junction

Abstract

The precise alignment of nerve terminals to postsynaptic specializations suggests that trans-synaptic cues direct synapse formation. As with much of our understanding of synaptic function, initial insight into both the presence and the identity of these synaptogenic cues was derived from studies at the vertebrate neuromuscular junction (NMJ), a synapse formed between motoneurons and skeletal muscle fibers. Unlike central synapses, the wide synaptic cleft of the NMJ contains a network of cell-associated extracellular glycoproteins in the form of a specialized basal lamina (BL). The discovery that components of this synaptic BL direct pre- and postsynaptic differentiation has fueled three decades of intense research on the molecular signals regulating NMJ formation. Here, in addition to describing the organization and morphological development of the vertebrate NMJ, the roles of these extracellular adhesion molecules in the formation, maturation, and maintenance of this synapse are discussed.