Axonal regeneration: Role of growth and guidance cues

During embryogenesis, developing axons are guided by a complex interplay of repellent and attractive molecules to establish functional connections with target regions. Axon guidance molecules, such as ephrins, semaphorins, slits, and netrins, but also morphogens and growth factors, participate in this process. Persistent repulsive guidance cues, myelin-derived outgrowth inhibitors, and lack of tropic factors are major factors creating a nonpermissive environment for axonal regeneration in the lesioned adult mammalian central nervous system. The modulation of inhibitory pathways and intrinsic proregenerative programs may thus be instrumental in therapeutic approaches for traumatic and degenerative neurological diseases.