Effect of peripheral nerve on limb development.

The effect of peripheral nerve on limb growth and maturation has received little attention after the limb differentiation stage. This study used an amphibian model (Rana pipiens) to examine the effect of temporary denervation on the development of limb muscle and bone tissues. Quantitative microscopic techniques were employed to evaluate bone and muscle size and cellularity between denervated and control limbs. A 15% decrease in tibial length and a 17% decrease in cross-sectional area were found in the temporarily denervated limbs as compared with the control limbs during the growing period studied. A 26% increase in tibial osteocyte density was found in the denervated limbs, although total osteocyte number was the same. The same differences were found on comparing less and more mature limbs from normal animals. Gastrocnemius muscle from temporarily denervated limbs had a 46% lesser cross-sectional surface area and a 66% greater muscle fiber density as compared with control limbs. Total muscle fiber number was the same. Similar findings were observed comparing limbs of different maturities from normal unoperated animals. This study suggests that the absence of peripheral nerves decreases the rate of bone maturation, which effect may be responsible for the diminished size of denervated limbs. This work demonstrates a model for regional growth disturbances that may aid in understanding such disorders as idiopathic leg length discrepancy, hemihypertrophy, clubfoot, and the limb deformities created by paralytic diseases.