Fig. 3.

Survival motor neuron (SMN) may be crucial for normal development and postnatal maintenance of the motor unit. In prenatal and perinatal stages, terminally differentiated motor neurons (MN) in the spinal cord express high levels of SMN. At these stages, developing motor axons are still small in diameter, but reach their target muscle correctly. The immature synaptic inputs in the spinal cord, as well as immature neuromuscular junctions (NMJs), are developing in neonatal stages. Once the motor unit is fully developed, SMN levels drop to normal levels. These levels are sufficient to maintain motor unit function and respond to nerve injury. In severe forms of spinal muscular atrophy (SMA; type 0 and 1), very low levels of SMN cause incomplete maturation of the motor unit. Classical features include incomplete development of synaptic inputs of motor neurons in the spinal cord and partial development of NMJs, eventually causing severe muscle weakness and premature death. In milder forms of SMA (types 2–4), the motor unit has completely developed, but SMN levels are too low to maintain structural and functional integrity of the motor unit. SMN levels are also too low to respond to nerve injury. Motor neuron loss and axonal degeneration eventually causes muscle weakness and atrophy