Journal article
DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans
RV da Silva, HC Johannssen, MT Wyss, RB Roome, FB Bourojeni, N Stifani, APL Marsh, MM Ryan, PJ Lockhart, RJ Leventer, LJ Richards, B Rosenblatt, M Srour, B Weber, HU Zeilhofer, A Kania
Cell Reports | CELL PRESS | Published : 2018
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 knock..
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Awarded by Fonds de Recherche du Québec - Santé
Funding Acknowledgements
Dcc<SUP>flox</SUP> 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 Quebec Sante - (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-Zurich 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.