Involvement of Rho-family GTPases in axon branching

Development of the nervous system requires efficient extension and guidance of axons and dendrites culminating in synapse formation. Axonal growth and navigation during embryogenesis are controlled by extracellular cues. Many of the same extracellular signals also regulate axonal branching. The emergence of collateral branches from the axon augments the complexity of nervous system innervation and provides an additional mechanism for target selection. Rho-family GTPases play an important role in regulating intracellular cytoskeletal and signaling pathways that facilitate axonal morphological changes. RhoA/G and Rac1 GTPase functions are complex and they can induce or inhibit branch formation, depending on neuronal type, cell context or signaling mechanisms. Evidence of a role of Cdc42 in axon branching is mostly lacking. In contrast, Rac3 has thus far been implicated in the regulation of axon branching. Future analysis of the upstream regulators and downstream effectors mediating the effects of Rho-family GTPase will provide insights into the cellular processes effected, and shed light on the sometimes opposing roles of these GTPases in the regulation of axon branching.