Defective Neuromuscular Synaptogenesis in Agrin-Deficient Mutant Mice

Defective Neuromuscular Synaptogenesis in Agrin-Deficient Mutant Mice

May 17, 1996 | Medha Gautam, Peter G. Noakes, Lisa Moscoso, Fabio Rupp, Richard H. Scheller, John P. Merlie, and Joshua R. Sanes
The study investigates the role of agrin in neuromuscular synapse formation using agrin-deficient mutant mice. Agrin, a protein synthesized and secreted by motoneurons, is known to trigger the formation of acetylcholine receptor (AChR) clusters on cultured myotubes. The researchers found that AChR aggregates are significantly reduced in number, size, and density in muscles of agrin-deficient mutant mice. This suggests that agrin is crucial for organizing postsynaptic differentiation. However, some postsynaptic differentiation still occurs in the mutant mice, indicating the presence of a second nerve-derived synaptic organizing signal. Additionally, intramuscular nerve branching and presynaptic differentiation are abnormal in the mutant mice, which may reflect either a distinct effect of agrin or impaired retrograde signaling from a defective postsynaptic apparatus. The study also reveals that axons can cluster AChRs to a limited extent in the absence of z-agrin, suggesting that other signals may play a role in this process. Furthermore, the presence of uninervated AChR clusters in mutant mice indicates that agrin may suppress the formation of ectopic clusters. The perturbation of axonal branching patterns in agrin-deficient muscle could be due to impaired retrograde signaling or a distinct effect of agrin. The study concludes that agrin is essential for organizing postsynaptic differentiation, but other signals may also contribute to this process.The study investigates the role of agrin in neuromuscular synapse formation using agrin-deficient mutant mice. Agrin, a protein synthesized and secreted by motoneurons, is known to trigger the formation of acetylcholine receptor (AChR) clusters on cultured myotubes. The researchers found that AChR aggregates are significantly reduced in number, size, and density in muscles of agrin-deficient mutant mice. This suggests that agrin is crucial for organizing postsynaptic differentiation. However, some postsynaptic differentiation still occurs in the mutant mice, indicating the presence of a second nerve-derived synaptic organizing signal. Additionally, intramuscular nerve branching and presynaptic differentiation are abnormal in the mutant mice, which may reflect either a distinct effect of agrin or impaired retrograde signaling from a defective postsynaptic apparatus. The study also reveals that axons can cluster AChRs to a limited extent in the absence of z-agrin, suggesting that other signals may play a role in this process. Furthermore, the presence of uninervated AChR clusters in mutant mice indicates that agrin may suppress the formation of ectopic clusters. The perturbation of axonal branching patterns in agrin-deficient muscle could be due to impaired retrograde signaling or a distinct effect of agrin. The study concludes that agrin is essential for organizing postsynaptic differentiation, but other signals may also contribute to this process.
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