23 Oral - Neurodevelopment I
Thursday April 07, 6:15 PM - 6:30 PM

Authors:
Ellie Heckscher ^{1, 2, 3}; Yi-wen Wang ^{1, 2, 3}; Chris Wreden ^{1, 2, 3}; Maayan Levy ^{2, 3, 4}; Zarion Marshall ¹

Affiliations:
1) University of Chicago, Chicago, IL, 60637; 2) Institute of Neuroscience; 3) Department of Molecular Genetics and Cell Biology; 4) Department of Neurobiology

Keywords:
o. stem cells; l. locomotion/flight

Neuronal stem cell lineages are fundamental developmental units of complex brains and neuronal circuits are the fundamental functional units. Understanding how circuits self-assemble starting from neuronal stem cells stem cells is still a largely un-answered developmental question with implications for neuroscience, evolution, and medicine. We use the Drosophila larval nerve cord as a model to study motor circuit assembly. Motor circuits are responsible for processing somatosensory stimuli and generating movement. In prior work, we found that neurons in a single lineage can be organized into groups called “temporal cohorts”. A temporal cohort is a set of neurons that are born during a small time window from a single stem cell and that have shared circuit level function (Wreden, et al., 2017, Meng, et al., 2019, Meng, et al., 2020). In this study, we ask how do neurons from different lineages wire with each other?

As a model, in segment A1 of the Drosophila larval nerve cord, we studied the NB3-3 lineage and the Even-skipped Lateral (EL) interneurons it produces. First, we used Twin-spot MARCM to determine the birth order and morphology of each EL. Then, we mined the Drosophila larval connectome to identify all major direct synaptic inputs onto ELs. Using graph theory, we found that early-born and late-born ELs get significantly different inputs. This supports the idea that early-born and late-born ELs are two temporal cohorts, as was proposed by Wreden et al., 2017. We next characterized the development and function of the circuit containing early-born ELs. early-born ELs get a majority of their input from just four classes of neurons: Chordotonal sensory neurons, Basin interneurons, Ladder interneurons, and EL interneurons segments other than A1. Anatomically, early-born ELs are embedded in a feed-forward motif, getting and functionally they act as on-set detectors for vibrational stimuli. Finally, we determined the developmental origins (e.g., stem cell parent and birth timing) of Ladders and Basins. Basins are a mid-late temporal cohort from the NB3-5 neuroblast, and Ladders are the only temporal cohort from the MNB neuroblast. Basins and Ladders synapse onto early-born ELs, and are born after early-born ELs. Together these data show: 1. Additional lineages are organized into temporal cohorts. 2. There is selective wiring among temporal cohorts. 3. Post-synaptic interneurons are born after their pre-synaptic interneuron partners. These data support a model in which a somatosensory stimulus on-set circuit develops by sequentially assembling a small subset of genetically pre-specified of temporal cohort units.