DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans
Summary: Avoidance of environmental dangers depends on nociceptive topognosis, or the ability to localize painful stimuli. This is proposed to rely on somatotopic maps arising from topographically organized point-to-point connections between the body surface and the CNS. To determine the role of top...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718300044 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Ronan V. da Silva Helge C. Johannssen Matthias T. Wyss R. Brian Roome Farin B. Bourojeni Nicolas Stifani Ashley P.L. Marsh Monique M. Ryan Paul J. Lockhart Richard J. Leventer Linda J. Richards Bernard Rosenblatt Myriam Srour Bruno Weber Hanns Ulrich Zeilhofer Artur Kania |
| spellingShingle |
Ronan V. da Silva Helge C. Johannssen Matthias T. Wyss R. Brian Roome Farin B. Bourojeni Nicolas Stifani Ashley P.L. Marsh Monique M. Ryan Paul J. Lockhart Richard J. Leventer Linda J. Richards Bernard Rosenblatt Myriam Srour Bruno Weber Hanns Ulrich Zeilhofer Artur Kania DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans Cell Reports |
| author_facet |
Ronan V. da Silva Helge C. Johannssen Matthias T. Wyss R. Brian Roome Farin B. Bourojeni Nicolas Stifani Ashley P.L. Marsh Monique M. Ryan Paul J. Lockhart Richard J. Leventer Linda J. Richards Bernard Rosenblatt Myriam Srour Bruno Weber Hanns Ulrich Zeilhofer Artur Kania |
| author_sort |
Ronan V. da Silva |
| title |
DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans |
| title_short |
DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans |
| title_full |
DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans |
| title_fullStr |
DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans |
| title_full_unstemmed |
DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans |
| title_sort |
dcc is required for the development of nociceptive topognosis in mice and humans |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-01-01 |
| description |
Summary: Avoidance of environmental dangers depends on nociceptive topognosis, or the ability to localize painful stimuli. This is proposed to rely on somatotopic maps arising from topographically organized point-to-point connections between the body surface and the CNS. To determine the role of topographic organization of spinal ascending projections in nociceptive topognosis, we generated a conditional knockout mouse lacking expression of the netrin1 receptor DCC in the spinal cord. These mice have an increased number of ipsilateral spinothalamic connections and exhibit aberrant activation of the somatosensory cortex in response to unilateral stimulation. Furthermore, spinal cord-specific Dcc knockout animals displayed mislocalized licking responses to formalin injection, indicating impaired topognosis. Similarly, humans with DCC mutations experience bilateral sensation evoked by unilateral somatosensory stimulation. Collectively, our results constitute functional evidence of the importance of topographic organization of spinofugal connections for nociceptive topognosis. : Da Silva et al. show that the axon guidance receptor DCC is necessary for the lateralization of spinothalamic projections. Mice lacking Dcc in the spinal cord have abnormal somatosensory cortex activation in response to noxious stimulation and fail to accurately localize noxious stimuli. DCC mutations in humans lead to mirroring of somatosensory stimuli. Keywords: topographic organization, nociception, spinothalamic, DCC, commissural, behavior, mutation, mirror movement disorder, pain, somatosensory system, human genetics |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718300044 |
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doaj-a9fcc6fbb25d459785e33a1569d7366c2020-11-25T00:27:31ZengElsevierCell Reports2211-12472018-01-0122511051114DCC Is Required for the Development of Nociceptive Topognosis in Mice and HumansRonan V. da Silva0Helge C. Johannssen1Matthias T. Wyss2R. Brian Roome3Farin B. Bourojeni4Nicolas Stifani5Ashley P.L. Marsh6Monique M. Ryan7Paul J. Lockhart8Richard J. Leventer9Linda J. Richards10Bernard Rosenblatt11Myriam Srour12Bruno Weber13Hanns Ulrich Zeilhofer14Artur Kania15Neural Circuit Development Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, CanadaInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, SwitzerlandInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, SwitzerlandNeural Circuit Development Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, CanadaNeural Circuit Development Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, CanadaNeural Circuit Development Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, CanadaBruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, AustraliaDepartment of Paediatrics, University of Melbourne, Parkville, VIC, Australia; Department of Neurology, University of Melbourne, Royal Children’s Hospital, Parkville, VIC, Australia; Neuroscience Research Group, Murdoch Children’s Research Institute, Parkville, VIC, AustraliaBruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, AustraliaDepartment of Paediatrics, University of Melbourne, Parkville, VIC, Australia; Department of Neurology, University of Melbourne, Royal Children’s Hospital, Parkville, VIC, Australia; Neuroscience Research Group, Murdoch Children’s Research Institute, Parkville, VIC, AustraliaThe University of Queensland, Queensland Brain Institute and School of Biomedical Sciences, St. Lucia, Brisbane, QLD, AustraliaDivision of Pediatric Neurology, Montreal Children’s Hospital, McGill University Health Centre (MUHC), and Departments of Pediatrics, Neurology and Neurosurgery, McGill University, Montreal, QC, CanadaDivision of Pediatric Neurology, Montreal Children’s Hospital, McGill University Health Centre (MUHC), and Departments of Pediatrics, Neurology and Neurosurgery, McGill University, Montreal, QC, CanadaInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, SwitzerlandInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, SwitzerlandNeural Circuit Development Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; Department of Anatomy and Cell Biology, Division of Experimental Medicine, McGill University, Montreal, QC, Canada; Corresponding authorSummary: Avoidance of environmental dangers depends on nociceptive topognosis, or the ability to localize painful stimuli. This is proposed to rely on somatotopic maps arising from topographically organized point-to-point connections between the body surface and the CNS. To determine the role of topographic organization of spinal ascending projections in nociceptive topognosis, we generated a conditional knockout mouse lacking expression of the netrin1 receptor DCC in the spinal cord. These mice have an increased number of ipsilateral spinothalamic connections and exhibit aberrant activation of the somatosensory cortex in response to unilateral stimulation. Furthermore, spinal cord-specific Dcc knockout animals displayed mislocalized licking responses to formalin injection, indicating impaired topognosis. Similarly, humans with DCC mutations experience bilateral sensation evoked by unilateral somatosensory stimulation. Collectively, our results constitute functional evidence of the importance of topographic organization of spinofugal connections for nociceptive topognosis. : Da Silva et al. show that the axon guidance receptor DCC is necessary for the lateralization of spinothalamic projections. Mice lacking Dcc in the spinal cord have abnormal somatosensory cortex activation in response to noxious stimulation and fail to accurately localize noxious stimuli. DCC mutations in humans lead to mirroring of somatosensory stimuli. Keywords: topographic organization, nociception, spinothalamic, DCC, commissural, behavior, mutation, mirror movement disorder, pain, somatosensory system, human geneticshttp://www.sciencedirect.com/science/article/pii/S2211124718300044 |