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Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all(More)
Recent studies suggest that glial cells actively participate in the formation, function, maintenance, and repair of the chemical synapse. However, the molecular mechanisms of glia-synapse interactions are largely unknown. We have shown previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis in Xenopus nerve-muscle cocultures. The(More)
Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in(More)
Glial cells are widely distributed throughout the nervous system, including at the chemical synapse. However, our knowledge of the role of glial cells at the synapse is rudimentary. Recent studies using a model synapse, the vertebrate neuromuscular junction (NMJ), have demonstrated that perisynaptic Schwann cells (PSCs), which are the glia juxtaposed to the(More)
Emerging studies demonstrate that perisynaptic Schwann cells (PSCs), which are the glia cells juxtaposed to the motor nerve terminal, actively participate in multiple aspects of the neuromuscular junction. During development, PSCs guide and promote synaptic growth. In adult muscles, PSCs can sense nerve stimulation by increasing intracellular calcium and(More)
Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular(More)
The vertebrate neuromuscular junction (NMJ) is a "tripartite" synapse, composed of three cellular elements: the presynaptic nerve terminal, the postsynaptic specialization, and synapse-associated glial cells, called perisynaptic Schwann cells (PSCs; also called terminal Schwann cells). During development, PSCs grow beyond nerve terminals and guide nerve(More)
Spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene, retention of the survival motor neuron 2 (SMN2) gene and insufficient expression of full-length survival motor neuron (SMN) protein. Quinazolines increase SMN2 promoter activity and inhibit the ribonucleic acid scavenger enzyme DcpS. The quinazoline derivative(More)
A number of mouse models for spinal muscular atrophy (SMA) have been genetically engineered to recapitulate the severity of human SMA by using a targeted null mutation at the mouse Smn1 locus coupled with the transgenic addition of varying copy numbers of human SMN2 genes. Although this approach has been useful in modeling severe SMA and very mild SMA, a(More)
Spinal Muscular Atrophy (SMA) is due to the loss of the survival motor neuron gene 1 (SMN1), resulting in motor neuron (MN) degeneration, muscle atrophy and loss of motor function. While SMN2 encodes a protein identical to SMN1, a single nucleotide difference in exon 7 causes most of the SMN2-derived transcripts to be alternatively spliced resulting in a(More)