@article{91058194f39a49db836e8fe28f5c9f66,
title = "DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans",
abstract = "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 = "DCC, behavior, commissural, human genetics, mirror movement disorder, mutation, nociception, pain, somatosensory system, spinothalamic, topographic organization",
author = "{da Silva}, {Ronan V.} and Johannssen, {Helge C.} and Wyss, {Matthias T.} and Roome, {R. Brian} and Bourojeni, {Farin B.} and Nicolas Stifani and Marsh, {Ashley P.L.} and Ryan, {Monique M.} and Lockhart, {Paul J.} and Leventer, {Richard J.} and Richards, {Linda J.} and Bernard Rosenblatt and Myriam Srour and Bruno Weber and Zeilhofer, {Hanns Ulrich} and Artur Kania",
note = "Funding Information: Dcc flox mice were a gift of F. Charron. We thank W. Boehlen, J. Cardin, M. Liang, and I. Kellenberger for technical assistance; M. Barrett for statistical analyses; R. Sharif, J.S. Mogil, E. Ruthazer, and S. Butler for comments on the manuscript; and our funding sources: a Merit Scholarship Program for Foreign Students (PBEEE) scholarship to R.V.S.; a Fonds de Recherche du Qu{\'e}bec - Sant{\'e} (FRQS) Scholarship to R.B.R.; an Australian Postgraduate Award to A.P.L.M.; a National Health and Medical Research Council (NHMRC) Career Development Fellowship ( GNT1032364 ) to P.J.L.; a Melbourne Children{\textquoteright}s Clinician Scientist Fellowship to R.J.L.; the Canadian Institutes of Health Research (CIHR) ( MOP-97758 ), the EJLB Foundation , The Quebec Pain Research Network , Brain Canada , the Canadian Foundation for Innovation , and W. Garfield Weston Foundation grants to A.K.; the Swiss National Science Foundation (SNSF) (grant 156393 ) to H.U.Z.; a McGill-Z{\"u}rich Collaboration grant to A.K. and H.U.Z.; and NHMRC Australia Project Grant ( GNT1059666 and GNT1126153 ), the Victorian Government{\textquoteright}s Operational Infrastructure Support Program and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS), and University of Zurich support of M.T.W. and B.W. The authors are very grateful to the families for their time and effort in being involved in this study as well as the support of the Australian Disorders of the Corpus Callosum (AusDoCC) support group. Funding Information: Dccflox mice were a gift of F. Charron. We thank W. Boehlen, J. Cardin, M. Liang, and I. Kellenberger for technical assistance; M. Barrett for statistical analyses; R. Sharif, J.S. Mogil, E. Ruthazer, and S. Butler for comments on the manuscript; and our funding sources: a Merit Scholarship Program for Foreign Students (PBEEE) scholarship to R.V.S.; a Fonds de Recherche du Qu{\'e}bec - Sant{\'e} (FRQS) Scholarship to R.B.R.; an Australian Postgraduate Award to A.P.L.M.; a National Health and Medical Research Council (NHMRC) Career Development Fellowship (GNT1032364) to P.J.L.; a Melbourne Children's Clinician Scientist Fellowship to R.J.L.; the Canadian Institutes of Health Research (CIHR) (MOP-97758), the EJLB Foundation, The Quebec Pain Research Network, Brain Canada, the Canadian Foundation for Innovation, and W. Garfield Weston Foundation grants to A.K.; the Swiss National Science Foundation (SNSF) (grant 156393) to H.U.Z.; a McGill-Z{\"u}rich Collaboration grant to A.K. and H.U.Z.; and NHMRC Australia Project Grant (GNT1059666 and GNT1126153), the Victorian Government's Operational Infrastructure Support Program and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS), and University of Zurich support of M.T.W. and B.W. The authors are very grateful to the families for their time and effort in being involved in this study as well as the support of the Australian Disorders of the Corpus Callosum (AusDoCC) support group. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = jan,
day = "30",
doi = "10.1016/j.celrep.2018.01.004",
language = "English",
volume = "22",
pages = "1105--1114",
journal = "Cell Reports",
issn = "2211-1247",
number = "5",
}