Sculpting the mature nervous system: Nuclear receptors shape connections by controlling degeneration and regeneration during development

Adult neurons in the CNS undergo little or no regeneration following insults such as spinal cord injury. Their inability to regenerate results from both non-cell autonomous negative signals as well as from reduced internal growth capabilities. In contrast, developing neurons are capable of extensive growth, extension and reorganization. However, it has long been challenged whether growth events during development resemble the regenerative process following injury. In my talk I will present unpublished data regarding a new pathway that we discovered, consisting of a nuclear receptor complex regulating the mTor kinase, as crucial for a regenerative process during neuronal remodeling of the Drosophila mushroom body (MB) neurons. Importantly, these nuclear receptors are not important for the initial growth of these or other types of neurons. Therefore, we discovered a pathway that is selectively required for regeneration during development. I will also provide evidence that the worm ortholog of Hr51, one of the nuclear receptors we identified, is required for injury induced regeneration following axotomy. Therefore, our data uncover a novel pathway regulating regeneration during development and following injury and suggest that developmental and injury induced axon regeneration share molecular similarities.