Insulin-like growth factor II gene expression: relationship to the development and regeneration of neuromuscular synapses.

The mechanisms responsible for the formation, loss, and regeneration of vertebrate synapses are still shrouded in mystery. Recent data suggesting that insulin-like growth factor II (IGF-II) may play a special role in the nervous system are reviewed. In particular, studies now show that the IGF-II gene is selectively expressed in a manner consistent with its involvement in the formation of the neural circuitry. The prenatal up-regulation and postnatal down-regulation of IGF-II transcripts in muscle are closely correlated with the prenatal accumulation and postnatal elimination, respectively, of polyneuronal innervation at the neuromuscular junction. Use and disuse of nerve and muscle can profoundly alter the developmental rate at which superfluous synapses are eliminated. Such alteration may result through modification of the rate at which postnatal down-regulation of IGF-II mRNA content occurs. Moreover, IGF-II mRNA content is correlated with the capacity of muscle to regenerate synapses. The IGF-II gene may be the first example of a gene which can regulate the development and turnover of vertebrate synapses.