GSE125490
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal
We utilized genetic methods to examine how Schwann cells prevent degeneration of motor neurons (MNs) in the spinal cord. Blocking peripheral, neuromuscular activity completely rescued MNs and neuromuscular junctions (NMJs) in erbB3 mutant mice lacking Schwann cells, which normally exhibit profound neurodegeneration. We searched for the molecular basis of this effect by examining the transcriptomes (all of the expressed genes) in the muscle of control mice with Schwann cells and erbB3 mutant mice without them. We found evidence that a negative signal expressed by muscle was regulated by neural activity and normally blocked by factors produced in Schwann cells.  When we eliminated this activity-induced negative signal (thrombin) from muscle, MNs and NMJs were protected in erbB3 mutants, similar to the effects of eliminating activity.  Together, these results suggest that Schwann cells prevent neurodegeneration by inhibiting the effect of activity-induced, muscle-derived negative factors, rather than by providing trophic positive factors. Overall design: 2 biological replicates of erbB3 WT, 2 biological replicates of erbB3 KO, and 2 biological replicates of Wnt1-Cre, Ribotag.