Molecular Control of Axon Branching

Axon branching is a complex morphological process, the regulation of which we are just beginning to understand. Many factors known to be important for axon growth and guidance have emerged as key regulators of axon branching. The extrinsic factors implicated in axon branching include traditional axon guidance cues such as the slits, semaphorins, and ephrins; neurotrophins such as BDNF; the secreted glycoprotein Wnt; the extracellular matrix protein anosmin-1; and certain transmembrane cell adhesion molecules-as well as sensory experience and neuronal activity. Although less is known about the intracellular control of axon branching, in recent years significant advances have been made in this area. Kinases and their regulators, Rho GTPases and their regulators, transcription factors, ubiquitin ligases, and several microtubule and actin-binding proteins are now implicated in the control of axon branching. It is likely that many more branching regulators remain to be discovered, as do the links between extrinsic cues and intracellular signaling proteins in the control of axon branching.