GDNF - A POTENT SURVIVAL FACTOR FOR MOTONEURONS PRESENT IN PERIPHERAL-NERVE AND MUSCLE

For survival, embryonic motoneurons in vertebrates depend on as yet un defined neurotrophic factors present in the limb bud. Members of the n eurotrophin family are currently the best candidates for such neurotro phic factors, but inactivation of their receptor genes leads to only p artial loss of motoneurons, which suggests that other factors are invo lved. Glial cell line-derived neurotrophic factor (GDNF), originally i dentified as a trophic factor specific for dopaminergic neurons, was f ound to be 75-fold more potent than the neurotrophins in supporting th e survival of purified embryonic rat motoneurons in culture. GDNF mess enger RNA was found in the immediate vicinity of motoneurons during th e period of cell death in development. In vivo, GDNF rescues and preve nts the atrophy of facial motoneurons that have been deprived of targe t-derived survival factors by axotomy. GDNF may therefore be a physiol ogical trophic factor for spinal motoneurons. Its potency and specific ity in vitro and in vivo also make it a good candidate for treatment o f motoneuron disease.