Understanding motoneurone development explains spinal muscular atrophy.

Studies of the organisation and function of the adult central nervous system (CNS) elucidated many basic properties of neurones and their interactions with each other. The present meeting illustrates the progress made during the past years in understanding the mechanisms involved in the processing of information by the CNS. Developmental biologists and neuroscientists are attempting to understand how this complex system has developed and what are the essential factors for establishing the networks seen in the adult. Recently much work has concentrated on studying the signals that induce the commitment of cells to the neuronal lineage, establish the identity of neurones and their initial connections with each other. Regarding the development of motoneurones and their connections with afferent signals recent results of Jessel and his colleagues has provided new and important information about the signalling molecules involved in this process (5). However, most of these studies are concerned with early developmental events, a period when the basic layout of the CNS and the connectivity between neurones as well as their peripheral targets is being established. Surprisingly in recent years there has been relatively little progress in understanding the events that take place after the basic layout of the CNS has been established. Yet, the developmental events during these periods are perhaps the most important for the evaluation of functional disturbances responsible for neuromuscular disorders that involve the motoneurone. One example of such a disorder is spinal muscular atrophy (SMA). In children suffering from this condition the basic ‘body plan’ at birth is not affected. It is possible that in cases where the development of the foetus is severely affected survival is impossible. Yet although some motoneurones die before birth, other components of the CNS are present, and their correct connections with each other are established, there is a devastating deterioration of the function of the neuromuscular system after birth. Here the possible implications of developmental events of the neuromuscular system that occur shortly before and immediately after birth for the pathogenesis of SMA will be considered.