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The Journal of Neuroscience, May 1, 2001, 21(9):3144-3150
Motoneuron Survival Is Enhanced in the Absence of Neuromuscular
Junction Formation in Embryos
J.
Terrado1,
R. W.
Burgess2,
T.
DeChiara3,
G.
Yancopoulos3,
J. R.
Sanes2, and
A. C.
Kato1
1 Division of Clinical Neuromuscular Research and
Department of Anesthesiology, Pharmacology and Surgical Intensive Care,
Faculty of Medicine, Centre Médical Universitaire, 1211 Geneva 4, Switzerland, 2 Department of Anatomy and
Neurobiology, Washington University Medical School, St. Louis, Missouri
63110, and 3 Regeneron Pharmaceuticals, Tarrytown, New York
10591
Approximately half of the motoneurons produced during development
die before birth or shortly after birth. Although it is believed that
survival depends on a restricted supply of a trophic sustenance
produced by the synaptic target tissue (i.e., muscle), it is unclear
whether synapse formation per se is involved in motoneuron survival. To
address this issue, we counted cranial motoneurons in a set of mutant
mice in which formation of neuromuscular junctions is dramatically
impaired (i.e., null mutants for agrin, nerve-derived agrin, rapsyn,
and MuSK).
We demonstrate that in the absence of synaptogenesis, there is an
18-34% increase in motoneuron survival in the facial, trochlear, trigeminal motor, and hypoglossal nuclei; the highest survival occurred
in the MuSK-deficient animals in which synapse formation is most
severely compromised. There was no change in the size of the mutant
motoneurons as compared with control animals, and the morphology of the
mutant motoneurons appeared normal. We postulate that the increased
axonal branching observed in these mutants leads to a facilitated
"access" of the motoneurons to muscle-derived trophic
factors at sites other than synapses or that inactivity increases the
production of such factors. Finally, we examined motoneurons in double
mutants of CNTFR  / (in which there is a partial loss
of motoneurons) and MuSK/ (in which there is an
increased survival of motoneurons). The motoneuron numbers in the
double mutants parallel those of the single MuSK-deficient mice,
indicating that synapse disruption can even overcome the deleterious
effect of CNTFR ablation.
Key words:
motoneuron survival; neuromuscular junction formation; null mutant mice; rapsyn; MuSK; agrin
Copyright © 2001 Society for Neuroscience 0270-6474/01/2193144-07$05.00/0
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