Abstract
BackgroundPeripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment. While damage to peripheral axons generally has a better outcome than injuries to central nervous system axons, it is currently unknown how neurons re-establish their target innervations to recover function after injury, and how accessory cells contribute to this task. Here we use a simple technique to create reproducible and localized injury in the posterior lateral line (pLL) nerve of zebrafish and follow the fate of both neurons and Schwann cells.ResultsUsing pLL single axon labeling by transient transgene expression, as well as transplantation of glial precursor cells in zebrafish larvae, we individualize different components in this system and characterize their cellular behaviors during the regenerative process. Neurectomy is followed by loss of Schwann cell differentiation markers that is reverted after nerve regrowth. We show that reinnervation of lateral line hair cells in neuromasts during pLL nerve regeneration is a highly dynamic process with promiscuous yet non-random target recognition. Furthermore, Schwann cells are required for directional extension and fasciculation of the regenerating nerve. We provide evidence that these cells and regrowing axons are mutually dependant during early stages of nerve regeneration in the pLL. The role of ErbB signaling in this context is also explored.ConclusionThe accessibility of the pLL nerve and the availability of transgenic lines that label this structure and their synaptic targets provides an outstanding in vivo model to study the different events associated with axonal extension, target reinnervation, and the complex cellular interactions between glial cells and injured axons during nerve regeneration.
Highlights
Peripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment
Reorganization of sensory innervation after pLL nerve regeneration To better understand how the reconnection of a functional sensory system is established after peripheral nerve degeneration/regeneration, we took advantage of the simple anatomical organization of the larval posterior lateral line in zebrafish
After 24 hpn in mutant fish, the regrowing axons strictly follow the aberrant route established during development, maintaining close contact with the chain of glial cells that lie along the way and reproducing the exact pattern of nerve branching observed after initial development of the tract (Figure 9B and D, arrowhead). These results suggest that Schwann cells provide an essential role in guidance of regenerating pLL axons and, in turn, that pLL axons serve as a substrate for Schwann cell precursor migration during embryonic stages and during peripheral nerve regeneration
Summary
Peripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment. While damage to peripheral axons generally has a better outcome than injuries to central nervous system axons, it is currently unknown how neurons re-establish their target innervations to recover function after injury, and how accessory cells contribute to this task. Injuries to peripheral nerves have a better prognosis [3] It is known from studies in the mouse that, after nerve injury, the distal portion of the nerve degenerates [4,5] and that, after about 1 week, the neurons start to regrow their axons from the proximal fragment [6,7]. In the peripheral nervous system, Schwann cells contribute greatly to axonal regeneration after nerve injury [10]. When Schwann cells are unable to dedifferentiate, they become less supportive of regeneration: myelin debris persists, neuronal death increases, and functional recovery is impaired [14,22]
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