The establishment of neuronal connections during development is a critical process for the correct function of central nervous system and for their regeneration during adult stages. Axon extension and guidance toward their targets are a complex process involving several signals provided by extracellular milieu where secreted factors, other cells, axons, and extracellular matrix proteins are interacting to establish the wiring of the brain. The expression of those signals at specific time and space, and their mechanisms of action during axon projection are the subject of numerous studies. This knowledge had contributed to understand the complex panorama of brain wiring during development and the origin and possible cure of central nervous system diseases. In this chapter, we focus on cell-cell and cell-matrix interactions as two important signals during axon guidance, and how these interactions impact the response to diffusible guidance cues. We emphasize the need and the challenge to understand the complex relations among simultaneous signals to guide axons projections, and how this knowledge could influence approaches to deal with neural regeneration issues.
Part of the book: Neurons