TY - JOUR
T1 - Defective neuromuscular synaptogenesis in agrin-deficient mutant mice
AU - Gautam, Medha
AU - Noakes, Peter G.
AU - Moscoso, Lisa
AU - Rupp, Fabio
AU - Scheller, Richard H.
AU - Merlie, John P.
AU - Sanes, Joshua R.
N1 - Funding Information:
We thank M. Nichol and J. Mudd for generation of chimeras; J. Cunningham, B. Klocke, and M. Elam for assistance; A. Nagy for R1 ES cells; Z. Hall and J. Sugiyama for anti-agrin antibodies; J. Lichtman for helpful comments; and G. Yancopolous for communicating results on MuSK prior to publication. We are especially grateful to M. Nichol for superb management of the animal facility during a difficult period. M. G. was a Fellow of the Myasthenia Gravis Foundation and P. G. N. was supported by the NH and Medical Research Council of Australia. This work was supported by grants from the National Institutes of Health and the Muscular Dystrophy Association (USA).
PY - 1996/5
Y1 - 1996/5
N2 - During neuromuscular synapse formation, motor axons induce clustering of acetylcholine receptors (AChRs) in the muscle fiber membrane. The protein agrin, originally isolated from the basal lamina of the synaptic cleft, is synthesized and secreted by motoneurons and triggers formation of AChR clusters on cultured myotubes. We show here that postsynaptic AChR aggregates are markedly reduced in number, size, and density in muscles of agrin- deficient mutant mice. These results support the hypothesis that agrin is a critical organizer of postsynaptic differentiation. However, some postsynaptic differentiation does occur in the mutant, suggesting the existence of a second nerve-derived synaptic organizing signal. In addition, we show that intramuscular nerve branching and presynaptic differentiation are abnormal in the mutant, phenotypes which may reflect either a distinct effect of agrin or impaired retrograde signaling from a defective postsynaptic apparatus.
AB - During neuromuscular synapse formation, motor axons induce clustering of acetylcholine receptors (AChRs) in the muscle fiber membrane. The protein agrin, originally isolated from the basal lamina of the synaptic cleft, is synthesized and secreted by motoneurons and triggers formation of AChR clusters on cultured myotubes. We show here that postsynaptic AChR aggregates are markedly reduced in number, size, and density in muscles of agrin- deficient mutant mice. These results support the hypothesis that agrin is a critical organizer of postsynaptic differentiation. However, some postsynaptic differentiation does occur in the mutant, suggesting the existence of a second nerve-derived synaptic organizing signal. In addition, we show that intramuscular nerve branching and presynaptic differentiation are abnormal in the mutant, phenotypes which may reflect either a distinct effect of agrin or impaired retrograde signaling from a defective postsynaptic apparatus.
UR - https://www.scopus.com/pages/publications/0029893117
U2 - 10.1016/S0092-8674(00)81253-2
DO - 10.1016/S0092-8674(00)81253-2
M3 - Article
C2 - 8653788
AN - SCOPUS:0029893117
SN - 0092-8674
VL - 85
SP - 525
EP - 535
JO - Cell
JF - Cell
IS - 4
ER -