Different genetic interactions effect distinct synaptic defects suggesting that distinct molecular aetiologies underlie ASD.

Abstract

<p><b>A.</b> The <i>Drosophila</i> NMJ contains presynaptic active zones (labelled by Bruchpilot, BRP) and postsynaptic glutamate receptor (labelled by GluRIIA). <b>B.</b> Representative images of BRP staining demonstrate a reduced number of active zone (BRP) puncta in the transheterozygotes <i>dlg/pak, NrxIV/dlg</i> and <i>NrxIV/pak</i> as compared to control (<i>w</i>^<i>1118</i>), <b>C.</b> The number of active zone (BRP) puncta (normalised to bouton size) were significantly reduced in <i>dlg/pak, NrxIV/Dlg</i> and <i>NrxIV/Pak</i> transheterozygotes. <b>D.</b> The fluorescence of the post-synaptic glutamate receptors were scored and normalised to bouton size HRP levels. <i>Pasha/Sep4</i> transheterozygotes were the only genotype to demonstrate decreased glutamate receptor abundance. <b>E.</b> Representative images of GluRIIA staining demonstrating the reduced fluorescence in the transheterozygote <i>Pasha/Sep4</i> when compared to control. <b>F.</b> A schematic showing the sub-types of genetic interactions supporting distinct molecular aetiologies underlying ASD that converge to yield defects at the synapse.</p