INTERCELLULAR COMMUNICATION THAT MEDIATES FORMATION OF THE NEUROMUSCULAR-JUNCTION

Reciprocal signals between the motor axon and myofiber induce structur al and functional differentiation in the developing neuromuscular junc tion (NMJ). Elevation of presynaptic acetylcholine (ACh) release on ne rve-muscle contact and the correlated increase in axonal-free calcium are triggered by unidentified membrane molecules. Restriction of axon growth to the developing NMJ and formation of active zones for ACh rel ease in the presynaptic terminal may be induced by molecules in the sy naptic basal lamina, such as S-laminin, heparin binding growth factors , and agrin. Acetylcholine receptor (AChR) synthesis by muscle cells m ay be increased by calcitonin gene-related peptide (CGRP), ascorbic ac id, and AChR-inducing activity (ARIA)/heregulin, which is the best-est ablished regulator. Heparin binding growth factors, proteases, adhesio n molecules, and agrin all may be involved in the induction of AChR re distribution to form postsynaptic-like aggregates. However, the strong est case has been made for agrin's involvement. ''Knockout'' experimen ts have implicated agrin as a primary anterograde signal for postsynap tic differentiation and muscle-specific kinase (MuSK), as a putative a grin receptor. It is Likely that both presynaptic and postsynaptic dif ferentiation are induced by multiple molecular signals. Future researc h should reveal the physiological roles of different molecules, their interactions, and the identity of other molecular participants.