Journal
NEUROSCIENCE
Volume 139, Issue 4, Pages 1385-1396Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2006.01.042
Keywords
Dab1; reeler; neuronal migration; dorsal horn; primary afferents; NK-1 receptor
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Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T34GM008563] Funding Source: NIH RePORTER
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Mutations in reeler, the gene coding for the Reelin protein, result in pronounced motor deficits associated with positioning errors (i.e. ectopic locations) in the cerebral and cerebellar cortices. In this study we provide the first evidence that the reeler mutant also has profound sensory defects. We focused on the dorsal horn of the spinal cord, which receives inputs from small diameter primary afferents and processes information about noxious, painful stimulation. We used immunocytochemistry to map the distribution of Reelin and Disabled-1 (the protein product of the reeler gene, and the intracellular adaptor protein, Dab1, involved in its signaling pathway) in adjacent regions of the developing dorsal horn, from early to late embryonic development. As high levels of Dabl accumulate in cells that sustain positioning errors in reeler mutants, our findings of increased Dabl immunoreactivity in reeler laminae I-III, lamina V and the lateral spinal nucleus suggest that there are incorrectly located neurons in the reeler dorsal horn. Subsequently, we identified an aberrant neuronal compaction in reeler lamina I and a reduction of neurons in the lateral spinal nucleus throughout the spinal cord. Additionally, we detected neurokinin-1 receptors expressed by Dab1-labeled neurons in reeler laminae I-III and the lateral spinal nucleus. Consistent with these anatomical abnormalities having functional consequences, we found a significant reduction in mechanical sensitivity and a pronounced thermal hyperalgesia (increased pain sensitivity) in reeler compared with control mice. As the nociceptors in control and reeler dorsal root ganglia are similar, our results indicate that Reelin signaling is an essential contributor to the normal development of central circuits that underlie nociceptive processing and pain. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.
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