Reelin dorsal horn neurons co‐express Lmx1b and are mispositioned in disabled‐1 mutant mice
| Autor: | Patricia E. Phelps, Carmine L. Chavez‐Martinez, Griselda M. Yvone, Deborah J. Wang, Amanda R. Nguyen |
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| Rok vydání: | 2020 |
| Předmět: |
Spinal Cord Dorsal Horn
Low-density lipoprotein receptor-related protein 8 Cell Adhesion Molecules Neuronal Nerve Tissue Proteins Biology Article Mice 03 medical and health sciences Glutamatergic 0302 clinical medicine Reeler Cell Movement medicine Animals Reelin 030304 developmental biology Neurons Extracellular Matrix Proteins 0303 health sciences General Neuroscience Serine Endopeptidases DAB1 Spinal cord Cell biology Posterior Horn Cells Reelin Protein medicine.anatomical_structure Nociception nervous system biology.protein Nucleus 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Eur J Neurosci |
| ISSN: | 1460-9568 0953-816X |
| Popis: | Mice missing either Reelin or Disabled-1 (Dab1) exhibit dorsal horn neuronal positioning errors and display heat hypersensitivity and mechanical insensitivity. Reelin binds its receptors, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, leading to the recruitment and phosphorylation of Dab1 and activation of downstream pathways that regulate neuronal migration. Previously, we reported that 70% of Dab1 laminae I-II neurons co-expressed LIM-homeobox transcription factor 1-beta (Lmx1b). Here, we asked whether Reelin-expressing dorsal horn neurons co-express Lmx1b, are mispositioned in dab1 mutants, and contribute to nociceptive abnormalities. About 90% of Reelin-labeled neurons are Lmx1b-positive in laminae I-II, confirming that most Reelin and Dab1 neurons are glutamatergic. We determined that Reelin-Lmx1b and Dab1-Lmx1b dorsal horn neurons are separate populations, and together, comprise 37% of Lmx1b-positive cells within and above the Isolectin B4 (IB4) layer in wild-type mice. Compared to wild-type mice, dab1 mutants have a reduced area of laminae I-II outer (above the IB4 layer), more Reelin-Lmx1b neurons within the IB4 layer, and fewer Reelin-Lmx1b neurons within the lateral reticulated area of lamina V and lateral spinal nucleus. Interestingly, both Reelin- and Dab1-labeled dorsal horn neurons sustain similar positioning errors in mutant mice. After noxious thermal and mechanical stimulation, Reelin, Lmx1b, and Reelin-Lmx1b neurons expressed Fos in laminae I-II and the lateral reticulated area in wild-type mice and, therefore, participate in nociceptive circuits. Together, our data suggest that disruption of the Reelin-signaling pathway results in neuroanatomical abnormalities that contribute to the nociceptive changes that characterize these mutant mice. |
| Databáze: | OpenAIRE |
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