PT - JOURNAL ARTICLE AU - Brandon Mark AU - Sen-Lin Lai AU - Aref Arzan Zarin AU - Laurina Manning AU - Albert Cardona AU - James W. Truman AU - Chris Q. Doe TI - The role of lineage, hemilineage and temporal identity in establishing neuronal targeting and connectivity in the <em>Drosophila</em> embryo AID - 10.1101/617936 DP - 2019 Jan 01 TA - bioRxiv PG - 617936 4099 - http://biorxiv.org/content/early/2019/04/24/617936.short 4100 - http://biorxiv.org/content/early/2019/04/24/617936.full AB - The mechanisms specifying neuronal diversity are well-characterized, yet it remains unclear how these mechanisms are used to establish neuronal morphology and connectivity. Here we map the developmental origin of over 78 neurons from seven identified neural progenitors (neuroblasts) within a complete TEM reconstruction of the Drosophila larval CNS. This allowed us to correlate developmental mechanism with neuronal projection and synapse targeting. We find that clonally-related neurons from individual neuroblasts project widely in the neuropil without preferential circuit formation. In contrast, the two NotchON/NotchOFF hemilineages from each neuroblast project to restricted dorsal/motor neuropil domains (NotchON) and ventral/sensory neuropil domains (NotchOFF). Thus, each neuroblast contributes both motor and sensory processing neurons, although they share little connectivity. Lineage-specific constitutive Notch transforms sensory to motor hemilineages, showing hemilineage identity determines neuronal targeting. Within a hemilineage, neurons of different temporal cohorts target their synapses to different sub-domains of the neuropil. Importantly, neurons sharing a sub-domain defined by hemilineage and temporal identity preferentially connect to neurons of another hemilineage/temporal profile. We propose that the mechanisms that generate neural diversity are also determinants of neural circuit formation.