title: Disabled-1 dorsal horn spinal cord neurons co-express Lmx1b and function in nociceptive circuits.
abstract: The Reelin-signaling pathway is essential for correct neuronal positioning within the central nervous system. Mutant mice with a deletion of Reelin, its lipoprotein receptors, or its intracellular adaptor protein Disabled-1 (Dab1), exhibit nociceptive abnormalities: thermal (heat) hyperalgesia and reduced mechanical sensitivity. To determine dorsal horn alterations associated with these nociceptive abnormalities, we first characterized the correctly positioned Dab1 neurons in wild-type and mispositioned neurons in Reelin-signaling pathway mutant lumbar spinal cord. Using immunofluorescence, we found that 70% of the numerous Dab1 neurons in Reln+/+laminae I-II and 67% of those in the lateral reticulated area and lateral spinal nucleus (LSN) co-express the LIM-homeobox transcription factor 1 beta (Lmx1b), an excitatory glutamatergic neuron marker. Evidence of Dab1- and Dab1-Lmx1b neuronal positioning errors was found within the isolectin B4 terminal region of Reln-/-lamina IIinner and in the lateral reticulated area and LSN, where about 50% of the Dab1-Lmx1b neurons are missing. Importantly, Dab1-Lmx1b neurons in laminae I-II and the lateral reticulated area express Fos after noxious thermal or mechanical stimulation and thus participate in these circuits. In another pain relevant locus - the lateral cervical nucleus (LCN), we also found about a 50% loss of Dab1-Lmx1b neurons in Reln-/-mice. We suggest that extensively mispositioned Dab1 projection neurons in the lateral reticulated area, LSN, and LCN and the more subtle positioning errors of Dab1 interneurons in laminae I-II contribute to the abnormalities in pain responses found in Reelin-signaling pathway mutants.
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Griselda M
authors.initials: GM
authors.lastname: Yvone
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Hannah H
authors.initials: HH
authors.lastname: Zhao-Fleming
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Joe C
authors.initials: JC
authors.lastname: Udeochu
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Carmine L
authors.initials: CL
authors.lastname: Chavez-Martinez
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hirose-Ikeda
authors.affiliation: Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
authors.forename: Patricia E
authors.identifier: 0000-0003-0735-5341
authors.initials: PE
authors.lastname: Phelps
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D059225:Nociception; D020671:Posterior Horn Cells / Q000378:metabolism* / Q000502:physiology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D014157:Transcription Factors; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Reeler mouse; lateral cervical nucleus; lateral spinal nucleus; neuronal migration disorders; pain