Developmentally Regulated Impediments to Skin Reinnervation by Injured Peripheral Sensory Axon Terminals

Catherina G Becker,Christian Söllner,Alvaro Sagasti,Carlos Portera-Cailliau,Seanna M Martin,Gavin J Wright,Georgeann S O'Brien

doi:10.1016/j.cub.2009.10.051

Catherina G Becker, Christian Söllner + Show 5 more

Open Access

https://doi.org/10.1016/j.cub.2009.10.051

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Abstract

SummaryThe structural plasticity of neurites in the central nervous system (CNS) diminishes dramatically after initial development, but the peripheral nervous system (PNS) retains substantial plasticity into adulthood. Nevertheless, functional reinnervation by injured peripheral sensory neurons is often incomplete [1–6]. To investigate the developmental control of skin reinnervation we imaged the regeneration of trigeminal sensory axon terminals in live zebrafish larvae following laser axotomy. When axons were injured during early stages of outgrowth, regenerating and uninjured axons grew into denervated skin and competed with one another for territory. At later stages, after the establishment of peripheral arbor territories, the ability of uninjured neighbors to sprout diminished severely, and although injured axons reinitiated growth, they were repelled by denervated skin. Regenerating axons were repelled specifically by their former territories, suggesting that local inhibitory factors persist in these regions. Antagonizing the function of several members of the Nogo Receptor (NgR)/RhoA pathway improved the capacity of injured axons to grow into denervated skin. Thus, as in the CNS, impediments to reinnervation in the PNS arise after initial establishment of axon arbor structure.

Highlights

It is well known that the primary axons of peripheral sensory neurons possess substantial regenerative capacity [reviewed in 1], few studies have examined the regenerative potential of unmyelinated axon terminals in the skin
We used zebrafish trigeminal neurons as a model to investigate the developmental regulation of cutaneous axon terminal plasticity and whether deficits in skin reinnervation may contribute to incomplete recovery following injury
To study the developmental control of skin reinnervation after injury, we severed the peripheral arbors of zebrafish trigeminal neurons expressing green fluorescent protein (GFP) with a femtosecond laser (Figure S1) [8], imaged their regeneration in live embryos for 12 hours, and traced their structure to quantify the success of target reinnervation (Figure 1 and supplemental movies)

Summary

The structural plasticity of neurites in the central nervous system (CNS) diminishes dramatically after initial development, but the peripheral nervous system (PNS) retains substantial plasticity into adulthood. Functional reinnervation by injured peripheral sensory neurons is often incomplete [1,2,3,4,5,6]. When axons were injured during early stages of outgrowth, regenerating and uninjured axons grew into denervated skin and competed with one another for territory. After the establishment of peripheral arbor territories, the ability of uninjured neighbors to sprout diminished severely, and injured axons reinitiated growth, they were repelled by denervated skin. As in the CNS, impediments to reinnervation in the PNS arise after initial establishment of axon arbor structure

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Discussion

Experimental Procedures