Formation and Maintenance of Neuromuscular Synaptic Connections Grant uri icon


  • Our previous work has shown that the glia (Schwann cells, SCs) at the neuromuscular junction (NMJ)participate in the removal of polyneuronal innervation during early postnatal development in mice. They do thisby interposing themselves between the nerve terminals and the muscle fibers and by phagocytosis of thenerve terminals themselves. However, what is unclear is what causes these SCs to behave in this destructivemanner. Our hypothesis is that some signal, likely from the nerve, engages this activity and thatthis signal is developmentally regulated. Here we propose a series of experiments that follow up on preliminaryresults that strongly suggest that the nerve membrane-linked isoform of a trophic factor called neuregulin 1type III might play this role. Schwann cells are known to be responsive to this signaling. We propose to uselight microscopy, electron microscopy, molecular biology, and physiology to examine the developmentalexpression of this isoform during early postnatal development and the consequences of manipulating theexpression of this isoform, and its receptor by use of transgenic and knockout mice. If our hypotheses arecorrect, then the display of neuregulin by motor axons to receptive SCs is at least part of the mechanismcontrolling the behavior of these cells at the synapse. Not only will these findings add to the existing knowledgeabout the roles of neuregulin in trophic maintenance and myelination activity of SCs, they will also suggestmechanisms by which these glial cells might participate in events that compromise synaptic function duringaging, neuromuscular disease, and repair of nerve injuries.

date/time interval

  • 2013 - 2020