The Role of DSCAMs in Synaptic Development in Drosophila

One long-standing hypothesis states that synaptic adhesion molecules, on pre- and post-synaptic neurons, provide a molecular “code” that determines whether a synaptic connection is established. However, the developmental role of many putative synaptic adhesion molecules remains relatively unexplored. Here we determine the role of Down syndrome cell adhesion molecules (DSCAM) in establishing correct synaptic connections within fruit fly, Drosophila melanogaster. Of the four DSCAM genes in Drosophila, only Dscam 1 has been determined to provide repulsive cues that prevent unintended synaptic connections. The role of Dscam 2, 3, and 4 remain undetermined. Our RNA sequencing data suggest that Dscam 2 is abundantly expressed between synaptic partners within a defined neural circuit. To investigate how the loss of DSCAM may alter connectivity, we use the Gal4/LexA system to selectively express Dscam 1-4 RNAi in synaptic partners. Following immunohistochemistry and confocal microscopy, we quantify changes in axon and dendrite area, length, location, and synaptic density. Studying the developmental role of DSCAM Drosophila may provide insight on how DSCAM overexpression contributes to neurodevelopmental defects in Down syndrome in humans.