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Abstract
Developing organisms use fine-tuning mechanisms to adjust body growth to ever-changing
nutritional conditions. In Drosophila, the secretory activity of insulin-producing
cells (IPCs) is central to couple systemic growth with amino acids availability. Here,
we identify a subpopulation of inhibitory neurons contacting the IPCs (IPC-connecting
neurons or ICNs) that play a key role in this coupling. We show that ICNs respond
to growth-blocking peptides (GBPs), a family of fat-body-derived signals produced
upon availability of dietary amino acids. We demonstrate that GBPs are atypical ligands
for the fly EGF receptor (EGFR). Upon activation of EGFR by adipose GBPs, ICN-mediated
inhibition of IPC function is relieved, allowing insulin secretion. Our study reveals
an unexpected role for EGF-like metabolic hormones and EGFR signaling as critical
modulators of neural activity, coupling insulin secretion to the nutritional status.