ABSTRACT
A major barrier to intraspinal regeneration after dorsal root (DR) injury is the DR entry zone (DREZ), the CNS/PNS interface. DR axons stop regenerating at the DREZ, even if regenerative capacity is increased by a conditioning lesion. This potent blockade has long been attributed to myelin-associated inhibitors and CSPGs, but incomplete lesions and conflicting reports have hampered conclusive agreement. Here we evaluated DR regeneration in adult mice, using novel strategies to facilitate complete lesions and comprehensive analyses, selective tracing of proprio-/mechanoreceptive axons with AAV2, and genetic or viral targeting of Nogo, MAG, OMgp, CSPGs and GDNF. Simultaneously eliminating Nogo/MAG/OMgp elicited little intraspinal penetration of DR axons, even with additional removal of CSPGs and a conditioning lesion. Their absence, however, synergistically enhanced GDNF-elicited intraspinal regeneration. We conclude that myelin inhibitors and CSPGs constrain intraspinal regrowth of DR axons, but that they are not the primary mechanism(s) stopping axons at the DREZ.
Competing Interest Statement
The authors have declared no competing interest.