# Mechanisms of early axonal pathfinding in the olfactory system of larval zebrafish

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $46,752

## Abstract

Abstract
In the olfactory system precise connections create a functional topographic map that translates odorant
experience into ordered patterns of odorant-specific neural activity. This map is established early in development.
Olfactory Sensory Neurons (OSNs) stochastically choose to mono-allelically express one Odorant Receptor
(OR), which belong to the G-Protein Coupled Receptor (GPCR) family, from a large gene repertoire. Each OSN
projects a single axon from the Olfactory Epithelium (OE) to the Olfactory Bulb (OB). Axons of OSNs first target
larger identifiable neuropils called protoglomeruli. In zebrafish, our lab has found that the protoglomerulus an
OSN axon targets correlates with the family or homology clade of its chosen OR. OSNs expressing ORs from
different homology clades target different protoglomeruli. Subsequent to this initial protoglomerular targeting,
the axons of OSNs expressing the same OR ultimately coalesce into smaller, distinct, and reproducible neuropil
regions known as glomeruli. Thus, the target location of each axon on the OB is coordinated with its chosen OR.
Previous research has shown that an OSN’s chosen OR and OR-driven neural activity are important for
glomerular segregation. However, it is not known how clade-specific protoglomerular targeting and OR-specific
glomerular segregation are achieved. Previous studies performed in the mouse may have conflated initial
targeting processes with glomerular segregation due to the relative inaccessibility of early developmental stages.
The foundational research in olfactory development utilized static imaging after development was complete,
often leading to developmental processes being inferred rather than investigated. We believe protoglomerular
targeting is determined by the coordinated expression of the OR locus and axon guidance loci, rather than OR
protein function. We have shown through single-cell RNA sequencing that OSNs expressing ORs within the
same homology clade also express similar transcription factors and axon-guidance-related factors. Further,
OSNs expressing closely related ORs target nearby glomeruli. Thus, I hypothesize that regulators controlling
OR choice in OSNs also regulate axonal guidance receptor expression, while OR-specific neural activity
regulates the subsequent segregation of OR-specific glomeruli. Utilizing a recombinase-mediated cassette
exchange approach, my proposed experiments will disambiguate the relative contributions of OR identity and
OR-driven neural activity to protoglomerular and glomerular targeting.

## Key facts

- **NIH application ID:** 10569006
- **Project number:** 5F31DC020111-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jessica Nicole Brandt
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569006

## Citation

> US National Institutes of Health, RePORTER application 10569006, Mechanisms of early axonal pathfinding in the olfactory system of larval zebrafish (5F31DC020111-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10569006. Licensed CC0.

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