In the developing embryo, 50% or more of the young motoneurons supplying the limb die. Amputation studies suggest that motoneurons depend on acquiring trophic factors from the limb. However, access to the trophic factors is under complex control since all motoneurons, whether destined to live or die, send axons into the limb. Axon invasion is not random but under the control of an axon guidance mechanism. Motoneurons probably compete for access to trophic factors at the neuromuscular junction. In order to compete, the motor axons must first be guided to specific limb regions. Failure causes death. Recent evidence suggests that motoneurons are specified for small localities within individual muscles and that the failure rate may be high enough to account for a large proportion of motoneuron deaths. The mechanisms of the implied recognition between motoneurons and muscles are unknown but may depend on positionally determined cell surface markers, histochemical compatibility, and functional congruence.
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