There are many fewer cell profiles per column, indicating reduced process formation (Figure 3B) and the cells have flattened as confirmed by reduction in the roundness index of cell profiles in vivo (Figure 3C). Flattening

and paucity of processes are also seen even in c-Jun−/− cells from neonatal nerves in vitro ( Figures 3D and 3E). Therefore, this is a robust phenotype that does not depend on long term denervation in vivo. Thus, c-Jun is an cell-intrinsic determinant of Schwann cell morphology check details that controls the structure of the essential regeneration tracks that guide growing axons back to correct targets. c-Jun specification of gene expression and morphology of denervated cells suggested that Schwann cell Dasatinib c-Jun might exert a decisive control over nerve repair. Because survival of injured neurons is the basis for repair, we measured the survival of small and large dorsal root sensory (DRG) neurons following sciatic nerve crush at the sciatic notch. We counted axons in L4 dorsal roots (Coggeshall et al., 1997) and the tibial nerve, and

neuronal somas and nucleoli in DRGs. Comparable results were obtained using all methods. Axon counts in WT dorsal roots showed that 20%–25% of the unmyelinated axons were lost following crush, as expected (Coggeshall et al., 1997). In contrast, 55%–60% of these axons were lost in c-Jun mutants, showing increased death of small DRG neurons in the mutant. This was confirmed by corrected (Abercrombie, 1946) counts of B neuron profiles in DRGs, showing 25%–30% loss in WT but 45%–65% loss in the mutants (Figures 4A and 4B). The number of myelinated

axons in dorsal roots remained unchanged in injured WT mice as expected (Coggeshall et al., 1997). But surprisingly, in the mutants the number of myelinated axons was reduced by 30%–35%, indicating death of large DRG cells. In confirmation, the corrected number of large A cell profiles in DRGs was reduced by about 40% in the mutants. The number of these profiles did not change significantly in injured WT (Figures 4C and 4D). We also carried out counts on DRG sections using nucleoli as the counted entity, an approach that theoretically provides the increased accuracy. Nucleoli in A type DRG neurons from uncut WT (n = 3), 10 week cut WT (n = 3), and 10 week cut c-Jun mutant (n = 3) mice were counted, corrected (Abercrombie, 1946), and expressed as percentage of uncut WT. This showed a 12% reduction in cut WT, (not significant; p > 0.40) but a 50% reduction in the c-Jun mutant (highly significant; p < 0.017). This provides a third line of evidence (in addition to counts of myelinated axons in dorsal roots and cell profiles) for the notion that nerve injury results in the loss of A type DRG neurons in mice that selectively lack c-Jun in Schwann cells.