Sensory axons must traverse a spinal cord glia limitans to connect the brain with the periphery. The fundamental mechanism of how these axons enter the spinal cord is still debatable; both Ramon y Cajal’s battering ram hypothesis and a boundary cap model have been proposed. To distinguish between these hypotheses, we visualized the entry of pioneer axons into the dorsal root entry zone (DREZ) with time-lapse imaging in zebrafish. Here, we identify that DRG pioneer axons enter the DREZ before the arrival of neural crest cells at the DREZ. Instead, actin-rich invadopodia in the pioneer axon are necessary and sufficient for DREZ entry. Using photoactivable Rac1, we demonstrate cell-autonomous functioning of invasive structures in pioneer axon spinal entry. Together these data support the model that actin-rich invasion structures dynamically drive pioneer axon entry into the spinal cord, indicating that distinct pioneer and secondary events occur at the DREZ.
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Spatial models of cell distribution in human lumbar dorsal root ganglia
Dorsal root ganglia (DRG), which contain the somata of primary sensory neurons, have increasingly been considered as novel targets for clinical neural interfaces, both for neuroprosthetic and pain applications. Effective use of either neural recording or stimulation technologies requires an appropriate spatial position relative to the target neural element, whether axon or cell body. However, the internal three‐dimensional spatial organization of human DRG neural fibers and somata has not been quantitatively described. In this study, we analyzed 202 cross‐sectional images across the length of 31 human L4 and L5 DRG from 10 donors. We used a custom semi‐automated graphical user interface to identify the locations of neural elements in the images and normalize the output to a consistent spatial reference for direct comparison by spinal level. By applying a recursive partitioning algorithm, we found that the highest density of cell bodies at both spinal levels could be found in the inner 85% of DRG length, the outer‐most 25–30% radially, and the dorsal‐most 69–76%. While axonal density was fairly homogeneous across the DRG length, there was a distinct low density region in the outer 7–11% radially. These findings are consistent with previous qualitative reports of neural distribution in DRG. The quantitative measurements we provide will enable improved targeting of future neural interface technologies and DRG‐focused pharmaceutical therapies, and provide a rigorous anatomical description of the bridge between the central and peripheral nervous systems.
more » « less- Award ID(s):
- 1653080
- NSF-PAR ID:
- 10458289
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Comparative Neurology
- Volume:
- 528
- Issue:
- 10
- ISSN:
- 0021-9967
- Page Range / eLocation ID:
- p. 1644-1659
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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