# Assembly of the Central Olfactory Networks in Drosophila

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $393,500

## Abstract

PROJECT SUMMARY
A central question in neurobiology is how individual neurons precisely connect with each
other to form functional circuits during development. Understanding the mechanisms of
neural circuit assembly may provide insights into the etiology of human brain disorders.
The fruit fly olfactory circuit has been an excellent model to investigate the mechanisms
by which wiring specificity of neural circuits arises during development. In this circuit,
axons of 50 types of olfactory receptor neurons (ORNs) match precisely with dendrites
of 50 corresponding types of second-order olfactory projection neurons (PNs), forming
50 discrete glomeruli in the antennal lobe. This allows olfactory information to be
faithfully delivered from peripheral sensory organs to higher brain centers, enabling
innate and learned olfactory behavior.
Thanks to the continual support of this grant since 2003, our studies have made the
Drosophila antennal lobe one of the best-understood circuits in the molecular, cellular,
and developmental underpinnings of wiring specificity. During the last grant cycle, we
made three key advances: 1) we determined single-cell transcriptomes of PNs and
ORNs across development, which have produced differentially expressed genes as
candidate wiring molecules and cell-type-specific drivers for labelling and genetically
manipulating individual PN and ORN types; 2) we developed a cell-surface proteomic
profiling method that allowed us to identify new wiring molecules; 3) we established an
explant culture that recapitulates wiring specificity in vivo, allowing us to examine the
dynamic process of circuit assembly in wild-type and mutants using time-lapse imaging.
In this proposal, we will take advantage of these advances to further investigate the
cellular and molecular mechanisms by which the olfactory circuit is assembled and
wiring specificity is achieved. Specifically, we will utilize new genetic tools and time-lapse
imaging to determine the cellular events that lead to PN dendrite patterning, segregation,
and ORN-PN synaptic partner matching. We will investigate the mechanisms by which
cell surface receptor teneurins work with putative ligands and downstream signaling
molecules to instruct synaptic partner matching. We will also identify additional
instructive wiring molecules and study their mechanisms of actions using data from
single-cell transcriptomes and in vivo assays that can distinguish attraction vs. repulsion
in ligand-receptor interactions.

## Key facts

- **NIH application ID:** 10792891
- **Project number:** 5R01DC005982-22
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** LIQUN LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,500
- **Award type:** 5
- **Project period:** 2003-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792891

## Citation

> US National Institutes of Health, RePORTER application 10792891, Assembly of the Central Olfactory Networks in Drosophila (5R01DC005982-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10792891. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*