RT Journal
A1 Bannerman, Peter
A1 James, Michelle A.
T1 Molecular Mechanisms to Improve Nerve Regeneration Following Damage to the Immature Peripheral Nervous System
JF The Journal of Bone & Joint Surgery
JO The Journal of Bone & Joint Surgery
YR 2009
FD July 1
VO 91
IS Supplement_4
SP 87
OP 89
DO 10.2106/JBJS.I.00279
UL http://dx.doi.org/10.2106/JBJS.I.00279
AB 
The dynamic interactions between motor nerve axons and skeletal muscle fibers have been well described. During late fetal and early postnatal human development, muscle tissue provides crucial trophic support to influence motor-neuron survival and differentiation. In return, motor-neuron innervation and activity provide signals that result in muscle growth and differentiation, including increased synthesis of contractile proteins, clustering of acetylcholinesterase at neuromuscular junctions, and the ultrastructural shaping of the mature neuromuscular junction. Early interactions between motor axons and muscles also prune multiple axonal inputs to each muscle fiber (polyneuronal innervation) to a one-to-one ratio between axon terminals and muscle fibers, thereby facilitating coordination between nerves and muscles. The loss of motor innervation during this critical period results in substantial loss of spinal cord motor neurons due to a lack of muscle-derived trophic support, preventing restoration of full muscle function1,2. Loss of muscle contraction during growth causes joint contractures3. Similar to motor axons, neonatal sensory neurons require trophic support (in particular, nerve growth factor) from target tissue. Interruption in the supply of this trophic support results in loss of a large proportion of neurons in the dorsal root ganglion, which inevitably restricts sensory reinnervation2. Loss of limb innervation in the fetal or perinatal period also results in reduced growth and development of bone, as evidenced by decreased size, incomplete formation of attachment sites for tendons, and the presence of osteoporosis and joint pathology, thus resulting in varying degrees of joint weakness associated with muscle paralysis and atrophy of the joint capsule3.