Overview

Once neurons are generated and have migrated to their final positions, two additional features pertinent to the adult organization of the nervous system must be established. First, different regions must be linked together via axon pathways. Second, orderly synaptic connections must be made among appropriate pre- and postsynaptic partners. The cellular mechanisms that generate axon outgrowth and synapse formation are thus the major determinants of neural circuitry. The directed growth of axons and the recognition of synaptic targets is mediated by a specialization at the tip of growing axons called the growth cone. Growth cones detect and respond to signaling molecules that identify intended pathways and ultimately facilitate correct synaptic partnerships. These signals include surface-bound and diffusible molecules that either attract or repel growing axons. In addition, secreted growth factors promote and maintain stable synapses in appropriate numbers between axons and their targets. As in other instances of intercellular communication, a variety of receptors and second messenger molecules transduce the signals provided to the growth cone and initiate the intracellular events that underlie directed growth and synapse formation. The end results of this dynamic signaling process are a wealth of well-defined peripheral and central axon pathways and detailed synaptic circuitry that allow animals to behave in ever more sophisticated ways as they mature.