Axon guidance: a balance between attraction and repulsion

Growing axons are guided by a variety of molecules which can either be diff usible or bound to a substrate or a membrane. Diffusible factors have been identified in several protein families, including the Netrins, Semaphorins, Neurotrophins, and Slit proteins, whose members can act as growth cone rep ellents or attractants, or, in some cases, both. Different classes of trans membrane receptors for these molecules have also been recently characterize d. An important emerging question is to understand what specifies the posit ive or negative response of a growth cone to a given diffusible factor. Rec ent studies have shown that transmembrane receptors, and more specifically their cytoplasmic domains, dictate whether a growth cone sees a cue as attr active or repulsive. In addition, studies of the cytoplasmic signal transdu ction pathways mediating repulsion and attraction in a variety of neurons a nd species indicate that the response of a growth cone depends on its activ ation state, and that many guidance molecules converge to the same signalin g pathways which can be modulated by cyclic nucleotides.