# Dynamic interactions among olfactory sensory neuron axons

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $414,849

## Abstract

Project Summary – Abstract
 Odor perception begins in the olfactory epithelium (OE) when ligands bind to molecular receptors
expressed on the cilia of the olfactory sensory neurons (OSNs). Buck and Axel (1991) were the first to
describe the large family of genes coding for the odorant receptors (ORs), now known to number ~1,200 in
mice. An OSN expresses only 1 OR. OSNs expressing the same OR do not cluster but rather are broadly
distributed across the OE. Thus, the OE is a complex mosaic of neurons each of which expresses only 1 of
1,200 possible ORs. As OSN axons exit the OE they initially fasciculate with nearest neighbors, not
necessarily with axons from OSNs expressing the same OR. However, as they progress over the surface
of the olfactory bulb to a point of glomerular convergence, the axons undergo a profound topographical
reorganization such that all of the axons coming from neurons expressing the same OR converge into only
2/3 glomeruli/olfactory bulb. This process of reorganization of axons and convergence into specific glomeruli
is broadly conserved among vertebrates and poses a significant wiring problem, perhaps the most complex
wiring problem found among sensory systems. Despite concerted efforts to identify the molecular substrates
of OSN axon growth, coalescence and targeting, we remain woefully ignorant of the most fundamental
aspects of axon:axon interactions: How does the reorganization of OSN axons relate to the organization of
their axoskeleton and organelles? What are the axoskeleton dynamics as axons initially fasciculate and
extend toward the OB and when they defasciculate in the olfactory nerve layer, forming new OR homotypic
fascicles targeted to specific glomerului? What drives fasciculation/defasciculation of OSN axons; are
mechanical forces involved? When do we recognize homotypic fasciculation? What is the timeline for the
maturation of OSNs and how does it relate to the extension of the axon to OB targets and functional
activity? Importantly, these fundamental questions apply equally to all vertebrates, in which olfactory system
development obeys the same basic rules. Thus here, in addition to studies of axon:axon interactions and
ultrastructure in mice, we introduce a new model, live imaging in zebrafish, to assess the dynamic nature of
OSN axon:axon interactions during development. To begin addressing these significant gaps in our
knowledge we propose 3 specific aims: Aim 1 - Test hypotheses regarding the cytoskeletal organization of
OSN axons and their fasciculation in the inner and outer sublaminae of the olfactory nerve layer of the
olfactory bulb. Aim 2 – Test the hypotheses that the axoskeleton dynamics, as well as mechanical forces,
control the fasciculation/defasciculation and navigation of OSN axons in the live zebrafish. Aim 3 – Test the
hypothesis that the spatio-temporal dynamics of OSN axon extension and the expression of cytoskeletal
and adhesion molecules differ in perinatal versus adult mice.

## Key facts

- **NIH application ID:** 10466784
- **Project number:** 5R01DC017989-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Charles A Greer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,849
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466784

## Citation

> US National Institutes of Health, RePORTER application 10466784, Dynamic interactions among olfactory sensory neuron axons (5R01DC017989-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10466784. Licensed CC0.

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