Axon Guidance by Growth Cones and Branches: Common Cytoskeletal and Signaling Mechanisms

Growing axons are guided to appropriate targets by responses of their motile growth cones to environmental cues. Interstitial axon branching is also an important form of axon guidance in the mammalian CNS. Visualization of growing axons in cortical slices and in dissociated cortical cultures showed that growth cone pausing behaviors demarcate sites of future axon branching. Studies of vertebrate and invertebrate growth cones suggest common mechanisms that regulate growth cone behaviors and axon branching. These include reorganization of the actin and microtubule cytoskeleton, dynamic interactions between microtubules and actin filaments, effects of axon guidance molecules, actions of actin regulatory proteins, and dynamic changes in intracellular calcium signaling. Future challenges will be to extend high-resolution imaging of single neurons to studies of intracellular events in the intact nervous system and to apply knowledge of developmental mechanisms to the promotion of axon sprouting after injury in the adult CNS.