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Peer-reviewedCC BYELife

Synaptic connectome of a neurosecretory network in the Drosophila brain

  • Theresa H. McKim1,2,3
  • Jayati Gera4,5,6
  • Ariana Julia B. Gayban7,2,3
  • Kevin Christie8,6
  • Joel Shin7,6
  • Nils Reinhard5,6
  • Giulia Manoli5,6
  • Selina Hilpert5,3
  • Patrick Callaerts9
  • Floris van Breugel8,2
  • Charlotte Helfrich‐Förster5
  • Meet Zandawala7,4,2,5
9 affiliations
  1. 1Department of Biology, University of Nevada Reno, Reno, 89557, NV, USA
  2. 2Integrative Neuroscience Program, University of Nevada Reno, Reno, 89557, NV, USA
  3. 3University of Nevada Reno
  4. 4Department of Biology, KU Leuven, 3000 Leuven, Belgium
  5. 5Neurobiology and Genetics, Theodor-Boveri Institute, Biocenter, University of Würzburg, 97074 Würzburg, Germany
  6. 6University of Wuerzburg
  7. 7Department of Biochemistry and Molecular Biology, University of Nevada Reno, Reno, 89557, NV, USA
  8. 8Department of Mechanical Engineering, University of Nevada Reno, Reno, 89557, NV, USA
  9. 9Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium
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Abstract

Hormones mediate inter-organ signaling which is crucial in orchestrating diverse behaviors and physiological processes including sleep and activity, feeding, growth, metabolism and reproduction. The pars intercerebralis and pars lateralis in insects represent major hubs which contain neurosecretory cells (NSC) that produce various peptide hormones. To obtain insight into how hormonal signaling is regulated, we have characterized the synaptic connectome of NSC in the adult Drosophila brain. Identification of neurons providing inputs to multiple NSC classes implicate diuretic hormone 44-expressing NSC as a major coordinator of physiology and behavior. Surprisingly, despite most NSC having dendrites in the subesophageal zone (primary taste processing center), inputs from peripheral gustatory neurons to NSC are largely indirect. We also deciphered pathways via which diverse olfactory inputs are relayed to NSC. Linear dynamical modeling of signal propagation through the connectome identifies enteric neurons as the strongest influencers of NSC activity compared to other sensory modalities. Further, our analyses revealed substantial inputs from brain descending neurons to NSC, suggesting that descending neurons regulate both endocrine and motor output to synchronize physiological changes with appropriate behaviors. In contrast to NSC inputs, synaptic output from NSC is sparse and mostly mediated by corazonin NSC. We show that both corazonin-expressing NSC and their downstream synaptic partner DNg27 influence egg-laying. We additionally explore putative paracrine interconnectivity between NSC classes and peptide hormone pathways from NSC to peripheral tissues by analyzing single-cell transcriptomic datasets. Our comprehensive characterization of the Drosophila neurosecretory network connectome provides a platform to understand complex hormonal networks and how they orchestrate animal behaviors and physiology.

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Cite

BibTeXRIS
BibTeX
@article{mckim2026synaptic,
  title = {{Synaptic connectome of a neurosecretory network in the Drosophila brain}},
  author = {Theresa H. McKim and Jayati Gera and Ariana Julia B. Gayban and Kevin Christie and Joel Shin and Nils Reinhard and Giulia Manoli and Selina Hilpert and Patrick Callaerts and Floris van Breugel and Charlotte Helfrich‐Förster and Meet Zandawala},
  journal = {ELife},
  year = {2026},
  month = oct,
  doi = {10.7554/elife.102684.3},
  url = {https://europepmc.org/article/PMC/PMC13657632},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Synaptic connectome of a neurosecretory network in the Drosophila brain
AU  - Theresa H. McKim
AU  - Jayati Gera
AU  - Ariana Julia B. Gayban
AU  - Kevin Christie
AU  - Joel Shin
AU  - Nils Reinhard
AU  - Giulia Manoli
AU  - Selina Hilpert
AU  - Patrick Callaerts
AU  - Floris van Breugel
AU  - Charlotte Helfrich‐Förster
AU  - Meet Zandawala
PY  - 2026
DA  - 2026/10/12
JO  - ELife
DO  - 10.7554/elife.102684.3
UR  - https://europepmc.org/article/PMC/PMC13657632
AB  - Hormones mediate inter-organ signaling which is crucial in orchestrating diverse behaviors and physiological processes including sleep and activity, feeding, growth, metabolism and reproduction. The pars intercerebralis and pars lateralis in insects represent major hubs which contain neurosecretory cells (NSC) that produce various peptide hormones. To obtain insight into how hormonal signaling is regulated, we have characterized the synaptic connectome of NSC in the adult Drosophila brain. Identification of neurons providing inputs to multiple NSC classes implicate diuretic hormone 44-expressing NSC as a major coordinator of physiology and behavior. Surprisingly, despite most NSC having dendrites in the subesophageal zone (primary taste processing center), inputs from peripheral gustatory neurons to NSC are largely indirect. We also deciphered pathways via which diverse olfactory inputs are relayed to NSC. Linear dynamical modeling of signal propagation through the connectome identifies enteric neurons as the strongest influencers of NSC activity compared to other sensory modalities. Further, our analyses revealed substantial inputs from brain descending neurons to NSC, suggesting that descending neurons regulate both endocrine and motor output to synchronize physiological changes with appropriate behaviors. In contrast to NSC inputs, synaptic output from NSC is sparse and mostly mediated by corazonin NSC. We show that both corazonin-expressing NSC and their downstream synaptic partner DNg27 influence egg-laying. We additionally explore putative paracrine interconnectivity between NSC classes and peptide hormone pathways from NSC to peripheral tissues by analyzing single-cell transcriptomic datasets. Our comprehensive characterization of the Drosophila neurosecretory network connectome provides a platform to understand complex hormonal networks and how they orchestrate animal behaviors and physiology.
SN  - 2050-084X
ER  -