Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity

Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell
proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector
Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury
to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repaircompetent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of
axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in
Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms
that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional
nerve repair in the PNS.