Attractive and repulsive signaling in nerve growth cone navigation

This chapter summarizes some of the putative signaling pathways that have been shown to participate in growth cone navigation. The function of the nervous system depends on complex and precise connections between nerve cells. The formation of specific connections during development often requires the growing axons to navigate over considerable distances to reach their final target cells. This long-range navigation is achieved by guidance factors within the developing tissue that regulate the motility or directionality of the growing tip of the axon, the growth cone. This chapter illustrates a general scheme of signal transduction cascades from the receptor activation to cytoskeletal rearrangements. Based on this, two types of guidance signals may be distinguished, signals that convey a "stop or go" command regulating growth cone motility, and signals that provide directional instructions to the growing axon, triggering turning responses of the growth cone. Axon guidance factors are multifunctional molecules capable of conferring attractive, repulsive, or stop signals. The precise behavior of a growth cone is determined by the nature of specific receptors and the status of cytoplasmic signal cascades, which are under the influence of a variety of extrinsic and intrinsic factors. An area of interest for future studies is determining the mechanisms that control or modulate the recruitment and activation of these cytoplasmic factors, and that amplify the signals conveyed by the receptors.