Artikel ; Online: Reelin dorsal horn neurons co-express Lmx1b and are mispositioned in disabled-1 mutant mice.
The European journal of neuroscience
2020 Band 52, Heft 5, Seite(n) 3322–3338
Abstract: 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 ... ...
| Abstract | 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. |
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| Mesh-Begriff(e) | Animals ; Cell Adhesion Molecules, Neuronal/genetics ; Cell Movement ; Extracellular Matrix Proteins/genetics ; Mice ; Nerve Tissue Proteins/genetics ; Neurons ; Posterior Horn Cells ; Reelin Protein ; Serine Endopeptidases ; Signal Transduction ; Spinal Cord Dorsal Horn | |||||
| Chemische Substanzen | Cell Adhesion Molecules, Neuronal ; Dab1 protein, mouse ; Extracellular Matrix Proteins ; Nerve Tissue Proteins ; Reelin Protein ; Reln protein, mouse (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-) | |||||
| Sprache | Englisch | |||||
| Erscheinungsdatum | 2020-08-09 | |||||
| Erscheinungsland | France | |||||
| Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. | |||||
| ZDB-ID | 645180-9 | |||||
| ISSN | 1460-9568 ; 0953-816X | |||||
| ISSN (online) | 1460-9568 | |||||
| ISSN | 0953-816X | |||||
| DOI | 10.1111/ejn.14847 | |||||
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| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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