Integrins at the neuromuscular junction are important for motoneuron survival

Abstract

During development motoneurons depend on target contact for their survival. Following injury to the sciatic nerve in neonatal rats, a large proportion of motoneurons die. However, the same injury inflicted at 5 days of age results in no loss of motoneurons. This critical period of postnatal development coincides with the time during which there is a significant increase in the release of transmitter from the nerve terminals at the neuromuscular junction. We have proposed that the role of the target muscle cell during this period is to induce this up-regulation of transmitter release from motor nerve terminals. It has been shown that stretch-induced increase in transmitter release from frog motor nerve terminals is accomplished via an integrin-dependent mechanism. In this study we examined the role of integrins at the rat neuromuscular junction in motoneuron survival. We found that blocking integrin binding at the developing neuromuscular junction delayed the increase in choline acetyltransferase activity that normally takes place during the early postnatal period, and resulted in motoneuron death. Furthermore, the maturation of those motoneurons that survived was delayed so they remained susceptible to subsequent nerve injury. These results support the possibility that integrins, by their involvement in modulating transmitter release, can influence motoneuron survival.