Background: Spinal muscular atrophy (SMA) is a genetic motor neuron disease caused by mutations in the SMN1 (Survival Motor Neuron) gene, which leads to hypotonia, muscle weakness and respiratory involvement. Its most severe form, SMA type 1, starts before 6 months of life has high mortality due ventilatory failure. Nusinersen, first approved treatment for SMA, an antisense oligonucleotide intr...

Clinical signs of upper motor neuron involvement are an essential observation to support the diagnosis of amyotrophic lateral sclerosis. However, clinical signs of upper motor neuron can be difficult to elicit in patients with motor neuron disease. One postulated reason for this problem is the presence of marked limb weakness and amyotrophy in motor neuron disease. This has been observed in pat...

LIM homeobox genes have a prominent role in the regulation of neuronal subtype identity and distinguish motor neuron subclasses in the embryonic spinal cord. We have investigated the role of Isl-class LIM homeodomain proteins in motor neuron diversification using mouse genetic methods. All spinal motor neuron subtypes initially express both Isl1 and Isl2, but Isl2 is rapidly downregulated by vi...

Motor neurons that control limb movements are organized as a neuronal nucleus in the developing ventral horn of the spinal cord called the lateral motor column. Neuronal migration segregates motor neurons into distinct lateral and medial divisions within the lateral motor column that project axons to dorsal or ventral limb targets, respectively. This migratory phase is followed by an aggregatio...

The SMN (survival motor neuron) gene plays an important role in ontogenesis and its dysfunction leads to immatu-rity of skeletal muscles and motor neurons in the spinal cord. As a result of SMN mutations the affected cells die and clinical symptoms of spinal muscular atrophy (SMA) develop. Physiologically, SMN together with gemins is part of a multiprotein complex of particular importance to mo...

Central nervous system GABAergic and glycinergic synaptic activity switches from postsynaptic excitation to inhibition during the stage when motor neuron numbers are being reduced, and when synaptic connections are being established onto and by motor neurons. In mice this occurs between embryonic (E) day 13 and birth (postnatal day 0). Our previous work on mice lacking glycinergic transmission ...

BACKGROUND Frontotemporal lobar degeneration with motor neuron disease (FTLD-MND) is a pathological entity characterized by motor neuron degeneration and frontotemporal lobar degeneration. The ability to detect the clinical signs of dementia and motor neuron disease in pathologically confirmed FTLD-MND has not been assessed. OBJECTIVES To determine if all cases of pathologically confirmed FTL...