Fig. 7. A proposed model for regulation of axon assembly of adult DRG neurons. To promote efficient axon growth, extracellular axon growth promoting factors are required. Adult naive neurons require the activation of both integrin and neurotrophin signaling pathways simultaneously for efficient axon growth. Both the CNS myelin-based inhibitor Nogo and glial scar-based inhibitor CSPGs can inhibit basal axon assembly by activation of Rho. However, CSPGs and myelin-based inhibitors act differently to affect axon growth when the extracellular axon growth promoting factors are present. CSPGs can interfere with ECM-integrin signaling, thus preventing extracellular factors from stimulating axon growth. On the contrary, activation of ECM-integrin pathway is able to antagonize the inhibitory effect of the myelin-based inhibitors. Peripheral nerve-injury-mediated conditioning lesion separates the neurotrophin and ECM-integrin pathways, thus allowing either ECM-integrin signaling or neurotrophin signaling to mediate axon assembly independently. As a result, neurotrophins can promote robust axon assembly of PCL neurons over CSPGs by bypassing the requirement of integrin activation for axon assembly.