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The role of lineage, hemilineage and temporal identity in establishing neuronal connectivity in the Drosophila larval CNS

By Brandon Mark, Sen-Lin Lai, Aref Arzan Zarin, Laurina Manning, Albert Cardona, James W Truman, Chris Q Doe

Posted 24 Apr 2019
bioRxiv DOI: 10.1101/617936

The mechanisms specifying neuronal diversity are well-characterized, yet it remains unclear how or if these mechanisms regulate neuronal morphology and connectivity. Here we map the developmental origin of 78 bilateral pairs of interneurons from seven identified neural progenitors (neuroblasts) within a complete TEM reconstruction of the Drosophila newly-hatched larval CNS. This allows us to correlate developmental mechanism with neuronal projections, synapse targeting, and connectivity. We find that clonally-related neurons from project widely in the neuropil, without preferential circuit formation. In contrast, the two NotchON/NotchOFF hemilineages from each neuroblast project to either dorsal motor neuropil (NotchON) or ventral sensory neuropil (NotchOFF). Thus, each neuroblast contributes both motor and sensory processing neurons. Lineage-specific constitutive Notch transforms sensory to motor hemilineages, showing hemilineage identity determines neuronal targeting. Within a hemilineage, temporal cohorts target processes and synapses to different sub-domains of the neuropil, effectively “tiling” the hemilineage neuropil, and hemilineage/temporal cohorts are enriched for shared connectivity. Thus, neuroblast lineage, hemilineage, and temporal identity progressively restrict neuropil targeting, synapse localization, and connectivity. We propose that mechanisms generating neural diversity are also determinants of neural circuit formation.

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