From neurite to nerve terminal: Induction of presynaptic differentiation by target-derived signals

The developing neuromuscular junction provides a simple system for understanding the cellular and molecular events that transform a growth cone into a nerve terminal. Molecules on the surface and within the extracellular matrix of the skeletal muscle cell provide cues for presynaptic differentiation which culminates in the development of presynaptic specializations. Growth factors bound to the heparan-sulfate proteoglycan on the muscle surface have been implicated as signals for the induction of these specializations. Upon reaching the target, the nerve may secrete a molecule to cause the local release of these factors, which then activate receptor tyrosine kinases on the neuronal membrane. This process may lend to the assembly of a cytoskeletal specialization to effect the clustering of synaptic vesicles and the organization of the presynaptic membrane.