Circuit architecture and regulation of the Drosophila brain neuroendocrine system

Insect neurosecretory cells (NSCs), located in distinct regions of the brain and the ventral nerve cord (VNC), are a major source of neuropeptides and peptide hormones (NPHs) that facilitate communication between the nervous system and peripheral tissues. NPHs, in turn, regulate growth and development, and modulate diverse behaviors and physiological processes including feeding, locomotion, social behaviors, metabolism, and reproduction. Given their central role in regulating systemic homeostasis, NSCs are tightly regulated. Recent advances in connectomics and single-cell transcriptomics have enabled comprehensive identification of NSCs in the Drosophila melanogaster brain and identified factors that modulate their activity. Here, we review the current state-of-the-art on insect NSCs and the inputs regulating them, predominantly focusing on adult Drosophila. We highlight: 1) major synaptic inputs, 2) neuromodulatory inputs, 3) gut-derived NPHs, and 4) cell-autonomous internal sensors that influence NSC activity. Finally, we discuss open questions in the field and how advances in omics approaches can bridge the gap in our understanding of NSC regulation between Drosophila and other insects.