Axon regeneration after spinal cord injury (SCI) is limited by both a decreased intrinsic ability of neurons to grow axons and the growth-hindering effects of extrinsic inhibitory molecules expressed around the lesion. Deletion of phosphatase and tensin homolog ( Pten ) augments mechanistic target of rapamycin (mTOR) signaling and enhances the intrinsic regenerative response of injured corticospinal neurons after SCI. Because of the variety of growth-restrictive extrinsic molecules, it remains unclear how inhibition of conserved inhibitory signaling elements would affect axon regeneration and rewiring after SCI. Moreover, it remains unknown how a combinatorial approach to modulate both extrinsic and intrinsic mechanisms can enhance regeneration and rewiring after SCI. In the present study, we deleted RhoA and RhoC , which encode small GTPases that mediate growth inhibition signals of a variety of extrinsic molecules, to remove global extrinsic pathways. RhoA / RhoC double deletion in mice suppressed retrac...