# Spatiotemporal mechanisms of in vivo axon initiation and targeting during development

> **NIH NIH F32** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $67,697

## Abstract

Project Summary
The nervous system regulates many aspects of animal behavior and physiology, and its function relies on the
generation of intricate networks of cellular connections. Failure to establish or maintain the proper connections
can have profound health consequences, including intellectual and developmental disabilities, requiring that
robust developmental mechanisms exist to ensure their precise organization. A common organizational motif in
nervous systems is the topographic map, in which the spatial relationships of neurons in a projecting field
matches the spatial organization of the target field. By leveraging the optical, embryological and genetic
accessibility of the zebrafish, we have discovered a novel temporal mechanism of topographic map formation
that is different from existing “chemoaffinity” models that involve the molecular matching of spatial coordinates.
Vagus motor axons emerge sequentially, with anterior axons emerging several hours earlier than posterior
axons. In a parallel temporally regulated process in the head periphery, pharyngeal arches appear in an
anterior-to-posterior appearance sequence. The outgrowing vagus axons then innervate the pharyngeal arches
sequentially from anterior to posterior, resulting in a topographic map in which anterior neurons innervate more
anterior targets and posterior neurons innervate more posterior targets. In this application, I propose to
investigate the molecular mechanisms underlying these two parallel temporal processes. In Aim 1 I will
determine how axon initiation is regulated at the cellular level in vivo, and will identify the differentially
expressed genes that promote axonogenesis in anterior vagus neurons and/or delay it in posterior neurons. In
Aim 2 I will investigate the role of the motor neuron chemoattractant HGF as the sequentially expressed
pharyngeal arch attractant that is required for vagus topographic mapping. This work will establish new
mechanisms that regulate axon specification and targeting, and will elucidate how the coordinated regulation of
temporal developmental events can guide the development of complex topographic maps in vivo.

## Key facts

- **NIH application ID:** 10077213
- **Project number:** 5F32HD096860-03
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Adam James Isabella
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $67,697
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077213

## Citation

> US National Institutes of Health, RePORTER application 10077213, Spatiotemporal mechanisms of in vivo axon initiation and targeting during development (5F32HD096860-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077213. Licensed CC0.

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