Preserve and protect: maintaining axons within functional circuits

•Pro-survival molecules protect axons from developmental pruning.•Apoptotic machinery mediates axonal pruning during development.•Lifelong axon maintenance requires proper mitochondrial and cytoskeletal function.•Impaired axon maintenance results in pathological axon degeneration.

During development, neural circuits are initially generated by exuberant innervation and are rapidly refined by selective preservation and elimination of axons. The establishment and maintenance of functional circuits therefore requires coordination of axon survival and degeneration pathways. Both developing and mature circuits rely on interdependent mitochondrial and cytoskeletal components to maintain axonal health and homeostasis; injury or diseases that impinge on these components frequently cause pathologic axon loss. Here, we review recent findings that identify mechanisms of axonal preservation in the contexts of development, injury, and disease.