GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle.
For survival, embryonic motoneurons in vertebrates depend on as yet undefined neurotrophic factors present in the limb bud. Members of the neurotrophin family are currently the best candidates for such neurotrophic factors, but inactivation of their receptor genes leads to only partial loss of motoneurons, which suggests that other factors are involved. Glial cell line-derived neurotrophic factor (GDNF), originally identified as a trophic factor specific for dopaminergic neurons, was found to be 75-fold more potent than the neurotrophins in supporting the survival of purified embryonic rat motoneurons in culture. GDNF messenger RNA was found in the immediate vicinity of motoneurons during the period of cell death in development. In vivo, GDNF rescues and prevents the atrophy of facial motoneurons that have been deprived of target-derived survival factors by axotomy. GDNF may therefore be a physiological trophic factor for spinal motoneurons. Its potency and specificity in vitro and in vivo also make it a good candidate for treatment of motoneuron disease.
INSERM U.382, IBDM, Marseille, France.
C E
CE
Henderson
H S
HS
Phillips
R A
RA
Pollock
A M
AM
Davies
C
C
Lemeulle
M
M
Armanini
L
L
Simmons
B
B
Moffet
R A
RA
Vandlen
L
L
Simpson LC corrected to Simmons
V E
VE
Koliatsos
A
A
Rosenthal
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D005145:Face / Q000294:innervation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006131:Growth Inhibitors / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects; D010525:Peripheral Nerves / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger