814C Poster - 13. Neural development and physiology
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Jake Henderson; Ellie Heckscher

Affiliation: University of Chicago

Keywords:
b. dendrites; h. intrinsic factors

For any animal to sense and interact with their environment, it is critical their neural circuits develop properly. The development of functioning neural circuits requires each neuron to correctly position its axonal and dendritic arbors and establish synaptic connections with their correct partners. Within neural circuits, interneurons are the most numerous cell type and are required for complex processing of sensory stimuli. Interneurons are an under investigated cell type due to the lack of tools and knowledge regarding neural circuit architecture within the CNS. In Drosophila, recent studies have clarified unique synaptic connections for many circuits, however how these connections are determined for interneurons is unclear. Temporal transcription factors and guidance cues are known to regulate neuronal development, however the role of these molecular factors has not been deeply investigated in interneuron dendrite development, synaptic partner selection, and circuit formation. We hypothesize that differential guidance receptor expression establishes specific dendritic morphologies and synaptic connections within interneurons born from the same stem cell. We investigated this hypothesis using the Drosophila melanogaster Neuroblast 3-3 stem cell lineage as a model. The NB3-3 lineage produces two cohorts of interneurons that create synaptic connections with two different sensory circuits: vibrational and proprioceptive. During development, the sensory neurons position their axons first at different locations within the ventral nerve cord. The two cohorts of even-skipped(+) lateral (EL) interneurons are then required to position their dendrites appropriately to receive the sensory input. We investigated the role of guidance receptors in interneuron dendrite morphogenesis by examining the expression pattern of Roundabout receptors within EL interneurons. We also examined the necessity and sufficiency of the Roundabout 3 (Robo3) receptor by manipulating its expression. These experiments revealed that Robo3 is involved in regulating EL interneuron dendrite position and therefore is a potential important factor in determining circuit wiring. This work will also enable future research to investigate the broad conservation of neuronal circuit specification and development of therapies for neurodevelopmental pathologies in which circuit wiring is disrupted.