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During development of higher vertebrates, many types of neurons including spinal and bulbar motoneurons are generated in excess. When developing motoneurons become postmitotic, they grow out axons and make contact with their target tissue, the skeletal muscle. Subsequently, about 50% of the motoneurons are lost during a critical process, which is called physiological motoneuron cell death. This phenomenon has been the focus of research for about a century and has led to the identification of neurotrophic factors that regulate survival of motoneurons during this developmental period. Motoneuron cell death is also observed in vitro when these neurons are isolated from the embryonic avian or rodent spinal cord. These cultured motoneurons have been a useful tool for studying basic mechanisms underlying neuronal degeneration. Such studies have revealed insights into signaling pathways that modulate survival during development and that might be disturbed under pathophysiological conditions in neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). However, specific differences in mechanisms that regulate survival of developing and postnatal motoneurons have also been identified. These findings could help to develop new therapeutic strategies that could counteract the pathophysiological processes underlying ALS.
Developmental motoneuron cell death
Viktor Hamburger and other pioneer researchers have shown during the first part of the twentieth century that the developmental cell death of motoneurons is guided by influences provided from the target tissue (Hamburger, 1934, 1958).
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