How sensory nerve endings in the skin interact with skin cells, such as epidermal keratinocytes, is a fundamentally understudied research area. This knowledge is however highly important as these interactions promote wound repair and limb regeneration, and their perturbations are known to lead to disease conditions like peripheral neuropathy. The Rieger lab is working on several questions with regard to axon-keratinocyte interactions:
- What type of interactions exist between somatosensory neurons and epidermal keratinocytes following tissue injury?
- What molecular processes promote their crosstalk?
- How are these molecular processes perturbed under disease conditions?
- Can we manipulate certain molecular pathways in neurons or keratinocytes to develop treatments for degenerative conditions leading to peripheral sensory axon degeneration (a type of peripheral neuropathy) and wound healing or appendage regeneration defects?
Dr. Rieger’s lab is using zebrafish as a model system to characterize sensory neuron-keratinocyte interactions in vivo, and they have recently begun to also investigate rodent models for comparative purposes. They focu primarily on mechanisms involving hydrogen peroxide (H2O2) signaling, as they identified this molecule to be a key mediator of the crosstalk between sensory neurons and keratinocytes following injury. Dr. Rieger’s lab discovered that H2O2 generated in wound keratinocytes promotes sensory axon regeneration (Rieger & Sagasti, PLoS Biology 2011). They also found evidence that hormetic concentrations of H2O2 are critical for proper wound repair. If the concentrations are too high, H2O2 can damage keratinocytes and induce wound healing defects. Similarly, they identified that high concentrations of H2O2 are induced in keratinocytes during treatment with the chemotherapeutic agent paclitaxel, leading to upregulation of the matrix-degrading metalloproteinase, MMP-13, in keratinocytes. Increased MMP-13 activity correlates with epidermal damage and sensory axon degeneration (Lisse et al., PNAS 2016).
Dr. Rieger’s lab has completed several studies to characterize the role of H2O2 in wound repair and are currently identifying H2O2-dependent molecular processes leading to sensory axon regeneration. They have also established zebrafish in vivo models with which to study the crosstalk between sensory neurons and keratinocytes under conditions of paclitaxel and glucose (diabetes) treatment.
Another project relates to the question how sensory nerve endings interact with wound epidermis following limb amputation. They are particularly interested in the role of Anterior Gradient Protein in this process, which has been shown to function in a nerve-dependent manner during newt limb regeneration. They are currently exploring the role of one family member of the Anterior Gradient Protein family in this process.