A Stem Cell Perspective on the Mechanisms Regulating Diversity and Complexity of the Higher Order Brain Centers

The insect central complex (CX) is an evolutionarily conserved neuropil that regulates diverse behaviors such as navigation, sleep homeostasis, and locomotion. The circuit motifs regulating discrete behaviors are composed of diverse neural types that arise from neural stem cells (NSCs) during development. Recent connectomics data suggests the adult Drosophila CX comprises 224 morphological and 262 connectivity neural types. Interesting questions in the field are; How do NSCs generate such amazing diversity, complexity and what developmental programs regulate neural circuit formation of the complex neural types? 
 
Most central complex lineages arise from the larval type II NSCs which generate intermediate neural progenitors to amplify and diversify lineages. In recent studies, we identified genes expressed in young and late-type II NSCs. Interestingly, steroid hormone signaling mediates early to late gene transition. Focusing on the neural types that regulate two essential behaviors, sleep and olfactory navigation, we have identified a unique type II NSC lineages that produce these distinct neural types. We show that most of the input neurons to sleep and olfactory navigation are generated by dorsolateral 1 DL1 NSC. Our studies show the NSC-specific temporal factor Imp, and ecdysone-induced E93 regulate the specification of ventral fan-shaped body input neurons and sleep-promoting dorsal fan-shaped body dFB neurons, respectively. The animals show defects in upwind olfactory navigation behavior upon type II NSC-specific Imp knockdown. Interestingly, the knockdown of late typeII NSC factor E93 affects sleep behavior. Our studies show NSC-specific programs regulating the neural identity and function of the neuron types regulating two essential behaviors.