Abstract:

Successful nerve regeneration requires not only that neurons reconstruct new axons distal to the site of injury, but also that those growing axons must navigate through the neuropil to make appropriate synaptic connections with target cells. While this is an imposing task for the thousands of axons that may occupy a regenerating nerve or central nervous system tract, the billions of neurons in the developing brain must accomplish similar tasks making connections that number in the trillions. How do neurons do this? One of the ways researchers have studied these questions is to introduce radiolabeled amino acids into cell bodies of neurons in anaesthetized, experimental animals during embryonic development or nerve regeneration. This in vivo approach labels newly synthesized proteins in the neuron, some of which are transported into the elongating axon. A similar approach has been used to investigate the possibility that RNA is transported axonally, substituting radiolabeled RNA precursors for amino acids. The original goal of these experiments was to explore the possibility that protein synthesis could occur locally in axons, the logic being that if proteins were being synthesized in axons, then the major stable RNAs (ribosomal and transfer RNAs) should be produced in the neuronal cell body and transported into the axon. These studies resulted in the surprising finding that in vertebrate neurons only a single species of RNA, 4S RNA (that co-migrated on SDS PAGE with 76nt, tRNA markers), could be demonstrated to be transported axonally, and only during axon growth (in regenerating optic axons of goldfish and sciatic nerves of rats), and during elongation of optic axons in developing rat and chick brains. Thus, the axonal transport of 76nt RNAs, parallels that of GAP-43.