REGULATION OF SPINAL MOTONEURON SURVIVAL BY GDNF DURING DEVELOPMENT AND FOLLOWING INJURY

During normal development of many vertebrate species, substantial numb ers of neurons in the central and peripheral nervous system undergo na turally occurring (or programmed) cell death. For example, approximate ly 50% of spinal motoneurons degenerate and die at a time when these c ells are establishing synaptic connections with their target muscles i n the chick, mouse, rat, and human. It is generally thought that the s urvival of developing motoneurons depends on access to trophic molecul es. Motoneurons that survive the period of programmed cell death may a lso die following injury in the developing or adult animal. Increasing evidence suggests that glial-cell-line-derived neurotrophic factor (G DNF) plays a physiological and/or pharmacological role in the survival of various neuronal cell types, including motoneurons. In this paper, we review the survival and growth-promoting effects of GDNF on spinal motoneurons during the period of programmed cell death and following injury.