Presented at the 2012 AAPM Annual Meeting « Back

Functions of Transcription Factor Sox11 in Axonal Growth, Target Innervations, and Neuropathic Pain

Lei Lei, PhD, llei@une.edu¹, Jennifer T. Malon, MS¹, Kyle S. Draleau, BS¹, Brady Butler, BS¹, Jordan Faloon, Undergraduate Student², Aubrey White, Undergraduate Student¹, Emilea Y. Lee, Undergraduate Student¹, Michael C. Anderson, Undergraduate Student¹, Ling Cao, MD PhD¹, Edward Bilsky, PhD¹, (1) University of New England, Biddeford, Maine, (2) ASPET, Biddeford, Maine

The transcription factor Sox11 is highly expressed in dorsal root ganglia during development. We demonstrated that Sox11 controls the survival and axonal growth of embryonic sensory neurons. In Sox11 null mice, sensory neurons undergo excessive cell death and display significantly reduced cutaneous projections. Sox11 is also one of the few transcription factors whose expression is highly up-regulated after peripheral nerve injury. We hypothesize that the upregulation of Sox11 is an adaptive change on the part of the nervous system to promote homeostasis and reinnervation of distal territories, thus protecting against the development of neuropathic pain. Alternatively, the upregulation of Sox11 may lead to transcriptional changes in nociceptors that contribute to pain hypersensitivity. To test these hypotheses, we generated nociceptor-specific Sox11 conditional knockout (CKO) mice using the Cre-loxP-mediated gene targeting system with the Nav1.8-Cre line that expresses Cre recombinase specifically in nociceptors. These CKO mice are viable and grossly normal. We are currently testing whether the upregulation of Sox11 after nerve injury is anti-nociceptive or pro-nociceptive in two nerve injury models - sciatic nerve crush which allows for nerve regeneration, and L5 spinal nerve transection which does not allow for nerve regeneration. We will determine whether Sox11 is required in nociceptors to promote axonal growth and target reinnervation post-nerve injury. These studies should provide insight into the pathophysiology of neuropathic pain states and suggest novel treatment strategies for prevention or reversal of these states. References: 1)Lin, L., Lee, V., Wang, Y., Lin, J., Sock, E., Wegner, M., and Lei, L. (2011). Sox11 regulates survival and axonal growth of embryonic sensory neurons. Developmental Dynamics 240, 52-64.

Funding: None