Poor regeneration of central nervous system (CNS) axons is a major obstacle for treating trauma and diseases. This is particularly true for retinal ganglion cells (RGCs) whose axons form the optic nerve. There are as yet no therapies to repair optic nerve once the damage is done. Our past studies have demonstrated that simultaneous modulation of genes and neurotrophic factors promotes long distance regeneration of some RGCs in adult mice. However, promoting axons not only to regenerate into the lesion, but to travel long distances and reconnect their central targets is still a major challenge. In fact, we and others have reported various degrees of axon misguidance where a few axons reinnervate brain targets while many fail to do so. It is unclear what cellular and molecular factors contribute to the limited (or successful) pathfinding and target reinnervation. At present, very little is known about axon guidance mechanisms in adult mammalian visual system after injury. Thus, one of the goals in my research is to examine the cellular and molecular factors that determine axon guidance and target selection during development and in adults after injury. Another goal of my research is to elucidate molecular mechanisms that underline axon regeneration failure. We and others have found that distinct proteins in mature neurons block axon regeneration. In new studies, I combine mouse genetics and bioinformatics and examine differential regenerative capacities among different RGCs and seek to delineate the molecular mechanisms that confer regeneration ability to select neuronal populations.