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

> **NIH NIH F32** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $2,500

## Abstract

Project Summary (From Parent Award)
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 innervous 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 archessequentially from anterior to
posterior, resulting in a topographic map in which anterior neurons innervate moreanterior 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:** 10401212
- **Project number:** 3F32HD096860-03S1
- **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:** $2,500
- **Award type:** 3
- **Project period:** 2021-05-04 → 2021-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401212

## Citation

> US National Institutes of Health, RePORTER application 10401212, Spatiotemporal mechanisms of in vivo axon initiation and targeting during development (3F32HD096860-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401212. Licensed CC0.

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