The axons of sensory neurons invade the epidermal layer of the skin to branch profusely between epithelial cells. Virtually every epithelial cell contacts sensory axons, and every axon contacts many epithelial cells. Our lab has uncovered several interactions between sensory axons and epithelial cells that regulate development and repair. For example, epidermal cells make molecules that guide axons to the skin, they clear debris from damaged sensory axons, release factors that promote axon regeneration, and wrap around sensory axons to seal them into ensheathment channels, similar to how glial cells wrap axons. Conversely, we found that sensory axons determine the distribution of cytoskeletal elements, lipids, and adhesion proteins in epithelial cell membranes. Ongoing studies address how axons migrate through the epithelium, how these interactions affect neuronal function, and how innervation impacts epithelial properties.

Projects

Microridge morphogenesis

Sensory neuron development and repair

Sensory neurons form elaborately branched peripheral axon arbors in the skin that detect pain and touch stimuli. Zebrafish sensory axons grow rapidly, and are the most superficial and earliest born neurons in the animal, making them ideal for live imaging and addressing universal questions about cellular processes in neurons. Our developmental studies have revealed how axons partition sensory territories in the skin, identified a pathway guiding axons to the skin, and revealed how sensory neurons remodel during metamorphosis. Using a laser to precisely cut axons, we have developed methods to study neuronal damage responses in live animals, revealing celllular processes and molecular pathways regulating axon degeneration and regeneration. Recently, we have begun studying how cytoskeletal organization regulates the elaborate morphologies of sensory axon arbors.

Cells make diverse protrusions that endow them with a vast variety of elaborate and beautiful forms. These protrusions are critical for cells to interact with and move through their environment. We study elongated protrusions called microridges, which form stunning maze-like patterns on mucosal epithelial cells, including those in the outer layer of the zebrafish skin. Our studies have revealed how cytoskeletal proteins and mechanical forces regulate microridge formation and organization. We have identified discrete steps in the process of microridge morphogenesis, and several new cytoskeletal regulatory proteins that function at each of those steps. Current projects focus on determining how cortical myosin contraction is regulated in space and time to promote mechanical conditions conducive to microridge development, and determining how additional cytoskeletal proteins regulate thier morphogenesis.

Neuron-skin cell interactions