Multiple modes and sites for the induction of axonal growth

Abstract

Nerve cells are usually at some distance from the cells they innervate (from a few microns to tens of centimeters). To reach their destination, nerve cells must make two major decisions. First, they must initiate axonal growth in order to reach their targets, and second, they must cease axonal growth after they have established synapses. The mechanisms involved in the decision-making process are not understood, and their elucidation represents a major challenge in neurobiology. This article suggests that nerve cells are in a state of dynamic equilibrium with regard to axonal growth. The processes leading to neurite extension are dependent on an inductive step(s) that involves either a stimulus for growth or the removal of an inhibitory influence. Similarly, the termination of growth depends on removal of the growth stimulus and/or exposure of the neuron to an inhibitory influence. These inductive steps may be provided by varying combinations of peripheral, central or transneuronal regulatory mechanisms to which nerve cells are continuously subjected. Therefore, it is the outcome of the ongoing interplay between multiple regulatory mechanisms that determines whether and to what extent neurons elongate their axons.