A recurrent observation in the development of the nervous system is the generation of neurons followed by their large scale elimination. This phenomenon, usually referred to as naturally occurring neuronal death, takes place at a particularly important time during the development of embryonic neurons-the period immediately followirig the arrival of their axons in the target fields. The extent of naturally occurring neuronal death varies considerably from region to region. In their seminal study of 1949, Viktor Hamburger and Rita Levi-Montalcini noted that the number of pyknotic(dying) neurons in the chick dorsal root ganglia that innervate a large peripheral field, such as the limb, is much smaller than the number of pyknotic neurons in ganglia innervating a small peripheral field, such as the neck and thorax. In addition, the degree of neuronal death can be dramatically increased by removing a prospective target early in development. In the absence of target, the number of neurons initially present is not changed, indicating that the target does not influence the number of neurons generated. Some of these target deprivation experiments were performed at the turn of the century, and their consequences on the development of neurons clearly reported. However, it took about 50 years to realize that, in fact, experimentally induced neuronal cell death merely exaggerates a phenomenon that is taking place during normal development(for a review of the slow maturation of this concept, see Oppenheim, 1981). Conversely, the degree of naturally occurring neuronal death can be decreased by adding an extra target or by blocking neurotransmission. For example, essentially all motoneurons can be rescued in chick embryos when paralyzed by applications of a-bungarotoxin or d-tubocurarine(Laing and Prestige, 1978; Pittman and Oppenheim, 1978). These observations demonstrate that the neurons normally eliminated are not programed to die, but can be rescued provided the conditions in which they grow are changed.

In vertebrates then, it seems that the fate of the neurons at the time of target innervation can be markedly influenced by epigenetic factors, with the target tissue apparently playing a major role in this regulation. Although neuronal death has been observed during development in a variety of invertebrates, the role played by the target is unclear. For example, in grasshopper embryos, many motoneurons die after sending their axons to the developing musculature. However, the early removal of the target limb bud in these embryos does not