835C Poster - 13. Neural development and physiology
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Dan Jindal ¹; Isabella Bacon ¹; Elizabeth Seitz ¹; Sugapradha Saravanan ¹; Alexis Bell ¹; Rhea Mahajan ²; Heather Broihier ¹

Affiliations:
1) Case Western Reserve University School of Medicine, Cleveland, OH; 2) Hathaway Brown School, Shaker Heights, OH

Keywords:
k. glia; c. innate immunity

Developing nervous systems initially form with an overabundance of synapses. The conserved process by which excess synapses are eliminated to yield mature nervous system circuitry is known as synaptic pruning. Beyond traditional supportive roles in neuronal homeostasis and function, glia are the primary effectors of synaptic pruning and clear synapses in part by phagocytosis. The mechanisms that tune glia-mediated synaptic pruning over development and adulthood are largely unclear.
Draper, an ortholog of Ced-1/MEGF10/Jedi, is the conserved surface receptor on glia that mediates engulfment and clearance in Drosophila. Glia require Draper to restrict presynapse number to normal levels in the adult antennal lobe. Directed screens are ongoing to reveal putative genes upstream of Draper that control the glial phagocytic program to allow for normal presynapse morphology. In tandem with this screen, it is important to assess (1) the effect of adult age on observed differences in presynapses between wild-type and candidate gene knockdown flies and (2) the split in pruning responsibility over time between two glial subtypes in direct contact with synaptic neuropil: astrocytes and ensheathing glia.
After this screen, it is crucial to characterize the effect of positive hits on the postsynaptic side of antennal lobe synapses. Beyond development, synaptic pruning is utilized by processes in the adult CNS like memory formation and maintenance. And so, the when and where of identified genes in regulating synapses is important; the developmental timing and the specific glia in which these genes act. Lastly, it is important to determine the functional impact of screened genes on adult olfaction and memory. Given that dysfunctional signaling between glia and synapses contribute to a host of synaptopathies, understanding the signaling pathways that direct the balance of synapse formation and removal is of significant therapeutic interest.