GDNF acts through PEA3 to regulate cell body positioning and muscle innervation of specific motor neuron pools.
Target innervation by specific neuronal populations involves still incompletely understood interactions between central and peripheral factors. We show that glial cell line-derived neurotrophic factor (GDNF), initially characterized for its role as a survival factor, is present early in the plexus of the developing forelimb and later in two muscles: the cutaneus maximus and latissimus dorsi. In the absence of GDNF signaling, motor neurons that normally innervate these muscles are mispositioned within the spinal cord and muscle invasion by their axons is dramatically reduced. The ETS transcription factor PEA3 is normally expressed by these motor neurons and fails to be induced in most of them in GDNF signaling mutants. Thus, GDNF acts as a peripheral signal to induce PEA3 expression in specific motor neuron pools thereby regulating both cell body position and muscle innervation.
Haase
Georg
G
INSERM U.382, Developmental Biology Institute of Marseille, CNRS-INSERM-Univ. Mediterranee, Campus de Luminy, Case 907, Marseille, France.
Dessaud
Eric
E
Garcès
Alain
A
de Bovis
Béatrice
B
Birling
Marie
M
Filippi
Pierre
P
Schmalbruch
Henning
H
Arber
Silvia
S
deLapeyrière
Odile
O
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation* / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C065788:transcription factor PEA3