Regenerative mechanisms of somatosensory neurons

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Project Summary/Abstract Adult neural stem cells give rise to newly formed neurons in discrete areas of the mammalian central nervous system. Whether adult neurogenesis occurs in the peripheral nervous system is unclear. We found a sparse cell type in the dorsal root ganglion (DRG) that expresses a growth factor shown to affect sensory neuronal survival and axonal regeneration in culture systems and by exogenous application to injured nerves. However, the endogenous source of this growth factor was unknown. Our discovery of this novel cell type suggests that the DRG itself is the source for this growth factor. We will test this idea in Aim 1. We propose to examine the function of this growth factor on sensory neuron viability in both naïve and injury contexts and axonal regeneration after injury through both loss and gain-of-function mouse models. In addition, we have reason to believe that the cell type expressing this growth factor may also have adult stem cell-like properties. In Aim 2, we will provide evidence for whether adult neurogenesis occurs in the DRG. We will examine whether neurons repopulate the DRG after injury, what types of DRG cells proliferate after injury long-term, and whether proliferation after injury is dependent on this growth factor. In addition, we will develop genetic tools to follow the lineage of the sparse cell type expressing this growth factor. Success in these Aims will provide evidence as to whether signaling through this growth factor or secretion of the growth factor through the sparse DRG cell type should be explored as a therapeutic strategy to support DRG cell viability, axonal regeneration, and perhaps neuronal regeneration of somatosensory neurons after peripheral nerve injury or in degenerative diseases.