Glial Wingless/Wnt Regulates Glutamate Receptor Clustering and Synaptic Physiology at theDrosophilaNeuromuscular Junction

Abstract

Glial cells are emerging as important regulators of synapse formation, maturation, and plasticity through the release of secreted signaling molecules. Here we use chromatin immunoprecipitation along with Drosophila genomic tiling arrays to define potential targets of the glial transcription factor Reversed polarity (Repo). Unexpectedly, we identified wingless (wg), a secreted morphogen that regulates synaptic growth at the Drosophila larval neuromuscular junction (NMJ), as a potential Repo target gene. We demonstrate that Repo regulates wg expression in vivo and that local glial cells secrete Wg at the NMJ to regulate glutamate receptor clustering and synaptic function. This work identifies Wg as a novel in vivo glial-secreted factor that specifically modulates assembly of the postsynaptic signaling machinery at the Drosophila NMJ.

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

“…Transmitter release at the Drosophila neuromuscular junction can be affected by the target muscle or the neighboring peripheral glia (Huang and Stern, 2002;Kerr et al, 2014;McCabe et al, 2003;Schmidt et al, 2012). RNAi-mediated atl knockdown in muscle or glia did not affect transmitter release or frequency of synaptic failures (Fig.…”

“…In particular, loss of activity within the peripheral glia of the kinesin heavy chain gene or the inebriated-encoded neurotransmitter transporter alters evoked transmitter release (Huang and Stern, 2002;Schmidt et al, 2012). In addition, the peripheral glia secrete at least two proteins, the TGF-β ligand Maverick and Wingless/Wnt, that regulate synaptic function (Fuentes-Medel et al, 2012;Kerr et al, 2014). The muscle, in turn, secretes the BMP ligand Gbb to regulate both evoked transmitter release and motor neuron arborization (McCabe et al, 2003).…”

Glial cells in neuronal development: recent advances and insights from Drosophila melanogaster

“…These synapses are glutamatergic, stereotypically positioned, and resemble mammalian central synapses in terms of the neurotransmitter used [50,51] . Compelling evidence has shown that glia, closely associated with these synapses, modulate synaptic activity and synapse formation [52][53][54][55][56] .…”

“…Wingless factor Reversed polarity (Repo), is secreted by glia to mediate postsynaptic glutamate receptor clustering [55] .…”

“…These synapses are glutamatergic, stereotypically positioned, and resemble mammalian central synapses in terms of the neurotransmitter used [50,51] . Compelling evidence has shown that glia, closely associated with these synapses, modulate synaptic activity and synapse formation [52][53][54][55][56] .Among the three types of peripheral glia, perineurial glia and SPGs, but not wrapping glia, send processes into the NMJ [56] . These processes display a variety of morphological structures along the motoneuron axons to the point of nerve-muscle contact, and sometimes extend into the proximal synaptic bouton, yet never completely cover the NMJ [5,53,56,57] .…”