Retrograde regulation of motoneuron differentiation by muscle beta-catenin.
Synapse formation requires proper interaction between pre- and postsynaptic cells. In anterograde signaling, neurons release factors to guide postsynaptic differentiation. However, less is known about how postsynaptic targets retrogradely regulate presynaptic differentiation or function. We found that muscle-specific conditional knockout of beta-catenin (Ctnnb1, also known as beta-cat) in mice caused both morphologic and functional defects in motoneuron terminals of neuromuscular junctions (NMJs). In the absence of muscle beta-catenin, acetylcholine receptor clusters were increased in size and distributed throughout a wider region. Primary nerve branches were mislocated, whereas secondary or intramuscular nerve branches were elongated and reduced in number. Both spontaneous and evoked neurotransmitter release was reduced at the mutant NMJs. Furthermore, short-term plasticity and calcium sensitivity of neurotransmitter release were compromised in beta-catenin-deficient muscle. In contrast, the NMJ was normal in morphology and function in motoneuron-specific beta-catenin-deficient mice. Taken together, these observations indicate a role for muscle beta-catenin in presynaptic differentiation and function, identifying a previously unknown retrograde signaling in the synapse formation and synaptic plasticity.
Li
Xiao-Ming
XM
Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
Dong
Xian-Ping
XP
Luo
Shi-Wen
SW
Zhang
Bin
B
Lee
Dae-Hoon
DH
Ting
Annie K L
AK
Neiswender
Hannah
H
Kim
Chang-Hoon
CH
Carpenter-Hyland
Ezekiel
E
Gao
Tian-Ming
TM
Xiong
Wen-Cheng
WC
Mei
Lin
L
D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000002:abnormalities* / Q000294:innervation* / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000002:abnormalities*; D009473:Neuronal Plasticity / Q000235:genetics; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D011940:Receptor Aggregation / Q000235:genetics; D011950:Receptors, Cholinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D051176:beta Catenin / Q000378:metabolism*
D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D051176:beta Catenin