Axon Regeneration in C. elegans : Genetics and Genomics

Regenerative regrowth of axons after damage is widespread throughout the animal kingdom. In adult mammals, extensive axon regeneration is possible in the peripheral nervous system, whereas the central nervous system has little or no regenerative capacity. Simple models of axon regeneration facilitate gene discovery and mechanistic studies of novel regulators of axon regeneration. The nematode C. elegans has highly stereotyped nervous system composed of 302 neurons that exhibits robust regeneration after laser axotomy. Key injury-induced signaling pathways such as the DLK-1 MAP kinase cascade play conserved roles in axon regeneration in C. elegans and in mammals. Large-scale screens have identified numerous regulators of gene expression as required for axon regeneration, including the CELF (CUGBP and Elav-like) family RNA-binding protein UNC-75 (Chen et al., 2011, Neuron 71: 1043). Genomic and transcriptomic analysis of UNC-75 targets in axon regeneration has revealed a conserved regulatory pathway required for efficient axon extension.