N-CADHERIN EXPRESSION IN DEVELOPING, ADULT AND DENERVATED CHICKEN NEUROMUSCULAR SYSTEM - ACCUMULATIONS AT BOTH THE NEUROMUSCULAR-JUNCTION AND THE NODE OF RANVIER

N-cadherin, a member of the Ca2+-dependent cell adhesion molecule fami ly plays essential roles in morphogenesis and histogenesis. N-cadherin has been shown in vitro to promote myoblast fusion and neurite outgro wth. We report here the cellular localization of N-cadherin during dev elopment and regeneration of the chick neuromuscular system. N-cadheri n was uniformly expressed along the surface of myoblasts and myotubes of E6 limb muscles. Later, as synaptogenesis and secondary myogenesis proceeded, N-cadherin expression was down-regulated and restricted to some large-diameter fibres, then to the areas of contact between few m yofibres and subsequently disappeared by embryonic day 17, suggesting that this cadherin may be implicated predominantly in fusion of primar y myoblasts and, at lower degree, of secondary myoblasts. The presence of N-cadherin in muscle during the period of nerve trunk ingrowth and its down-regulation after synaptogenesis suggests that this molecule might be implicated in both processes. N-cadherin became accumulated a t the neuromuscular junction only a few days after the first synaptic contacts were established and remained at the adult neuromuscular junc tion, suggesting a role of this molecule in the stabilization of the m ature neuromuscular junction. In sciatic nerve, the level of N-cadheri n expression remained unchanged from hatching to adult life. N-cadheri n was widely distributed on the surface of myelinated fibres and on my elinating Schwann cells: in addition, it was concentrated at the node of Ranvier. At the ultrastructural level, the molecule was detected in side, at the surface and in the basal lamina of Schwann cells and also associated with endoneurial collagen. These observations suggest a ro le of N-cadherin in the structuring and stabilization of the myelin sh eaths. After nerve injury, N-cadherin continued to be expressed by pro liferating Schwann cells in the distal stump providing a substratum fo r regenerating axons. N-cadherin reappeared at the surface of denervat ed muscle fibres without disappearing from the former synaptic sites. It was detected not only in the sarcoplasm and on sarcolemma of denerv ated muscle fibres, but also in the basal lamina and in the extracellu lar matrix. The reexpression of N-cadherin at the surface of denervate d muscle fibres suggests a role for this molecule in muscle reinnervat ion. The presence of N-cadherin in basal lamina and its association wi th collagen fibres raise questions about the release of N-cadherin in the extracellular space and the existence of a putative heterophilic l igand for N-cadherin.