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Walker Lab
Geisel School of Medicine at Dartmouth
Finding the correct target: Axon guidance and synapse formation from development to regeneration
The 5 day old larval zebrafish pectoral fin is an ideal system to study axon targeting. Muscles are shown in orange, motor nerves are blue, and synapses are in magenta. Each nerve contains many axons, which all target specific muscle fibers. Remarkably, after injury these axons return back to their original muscle fibers. Did you move today? Our brains control our movements by sending electrical signals to our muscles causing them to contract. These signals travel via specialized neuronal structures called axons, which wire the nervous system. Each axon has to connect to the correct muscle to enable coordinated movement. If axons become damaged, like after traumatic injury, movement is lost. Fortunately, in the peripheral nervous system, axons can regenerate, but often they find the wrong muscle targets, leading to functional deficits. Despite its clinical relevance, the cues that enable precise axonal targeting during regeneration are largely unknown.
Our model system is the zebrafish pectoral fin, which is innervated by dozens of motor axons that target specific muscle fibers. After injury, these axons regenerate back to their original targets via unknown mechanisms.
The Walker lab seeks to identify the cellular and molecular mechanisms of how axons find their muscle targets. We use genetic, molecular, and live-imaging to study regulators of axon guidance. We will couple these techniques with single-cell and spatial transcriptomics to map the molecular cues that enable precise innervation.