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| Item Type: | Article |
|---|---|
| Title: | Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance |
| Creators Name: | Fricker, F.R., Zhu, N., Tsantoulas, C., Abrahamsen, B., Nassar, M.A., Thakur, M., Garratt, A.N., Birchmeier, C., McMahon, S.B., Wood, J.N. and Bennett, D.L. |
| Abstract: | Neuregulin-1 has a key role in mediating signaling between axons and Schwann cells during development. A limitation to studying its role in adulthood is the embryonic lethality of global Nrg1 gene deletion. We used the Cre-loxP system to generate transgenic mice in which neuregulin-1 is conditionally ablated in the majority of small-diameter and a proportion of large-diameter sensory neurons that have axons conducting in the C- and Adelta-fiber range, respectively. Sensory neuron-specific neuregulin-1 ablation resulted in abnormally large Remak bundles with axons clustered in "polyaxonal" pockets. The total number of axons in the sural nerve was unchanged, but a greater proportion was unmyelinated. In addition, we observed large-diameter axons that were in a 1:1 relationship with Schwann cells, surrounded by a basal lamina but not myelinated. There was no evidence of DRG or Schwann cell death; the markers of different DRG cell populations and cutaneous innervation were unchanged. These anatomical changes were reflected in a slowing of conduction velocity at the lower end of the A-fiber conduction velocity range and a new population of more rapidly conducting C-fibers that are likely to represent large-diameter axons that have failed to myelinate. Conditional neuregulin-1 ablation resulted in a reduced sensitivity to noxious mechanical stimuli. These findings emphasize the importance of neuregulin-1 in mediating the signaling between axons and both myelinating and nonmyelinating Schwann cells required for normal sensory function. Sensory neuronal survival and axonal maintenance, however, are not dependent on axon-derived neuregulin-1 signaling in adulthood. |
| Keywords: | Analysis of Variance, Axons, Calcitonin Gene-Related Peptide, Cultured Cells, Electric Stimulation, Gene Expression Regulation, In Situ Nick-End Labeling, Indoles, Knockout Mice, Lectins, Mammalian Embryo, NAV1.8 Voltage-Gated Sodium Channel, Nerve Fibers, Nerve Tissue Proteins, Neural Conduction, Neuregulin-1, Neurofilament Proteins, Neuroglia, Newborn Animals, Pain Measurement, Pain Threshold, Physical Stimulation, Reaction Time, Schwann Cells, Sensation, Sensory Receptor Cells, Signal Transduction, Skin, Sodium Channels, Spinal Ganglia, Sural Nerve, Transmission Electron Microscopy, Animals, Mice |
| Source: | Journal of Neuroscience |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Volume: | 29 |
| Number: | 24 |
| Page Range: | 7667-7678 |
| Date: | 17 June 2009 |
| Additional Information: | Copyright (c) 2009 by The Society for Neuroscience |
| Official Publication: | https://doi.org/10.1523/JNEUROSCI.6053-08.2009 |
| PubMed: | View item in PubMed |
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