Yimin Zou, University of California San Diego, San Diego, USA

Role of Wnt-Ryk signaling in corticospinal tract regeneration after spinal cord injury

Funded in: 2011, 2012

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During the development and maturation of neural circuits molecular signals navigate the axons to their targets. Axon guidance molecules like the Wnt proteins are potent regulators of axon growth and controls the direction of both sensory and motor axon tracts in the spinal cord during development. Wnt signalling is a delicate balance between both attraction and repulsion mediated through different receptors, via the attracting receptor, Frizzled3, and via the repulsive Wnt-binding receptor, Ryk.

In normal adult spinal cord, Wnts and their receptors are no longer expressed. But it was shown that following spinal cord injury, the Wnt system was reinduced and Wnt-Ryk signaling caused the retraction/dying back of corticospinal axons, further hindering repair. Inhibiting Ryk with antibodies prevented axon retraction and promoted sprouting of collateral branches. Therefore, the project aims to fully characterize how Wnt-Ryk signaling mediates retraction of corticospinal tract axons in the adult spinal cord following injury.

As inhibition of repulsive Wnt signaling holds great promise as a therapeutic approach to axon regeneration, there is the plan to develop a monoclonal antibody against Ryk in order to promote regeneration of both sensory and motor pathways as well as test a combinatorial approach of modulating Wnt signaling.