# Molecular pathways underlying organ-specific targeting by the vagus nerve

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2020 · $67,446

## Abstract

PROJECT SUMMARY / ABSTRACT
The long-term goal of this project is to reveal basic neurobiological mechanisms about how vagal sensory
neurons find, innervate, and interact with specific end-organs and tissues during development. Sensory
neurons of the vagus nerve detect and transmit diverse signals from internal organs, including ingested
nutrients, changes in blood pressure, and mechanical distension of the stomach. Anatomically, it is a uniquely
long cranial nerve that emanates from a single pair of ganglia near the hindbrain yet courses through the entire
body and innervates a myriad of target tissues. From these ganglia, each vagal sensory neuron sprouts a
single pseudounipolar axon that targets a specific internal organ peripherally and a dedicated brainstem circuit
centrally. Faithfully establishing this connectivity is essential for neural control of physiological functions such
as breathing, heart rate and digestion. Despite its vital role and the emerging importance of brain-viscera
communication, it remains largely unknown how the intricate anatomical structure of the vagus nerve forms
during development, and whether miswiring of the vagus nerve may contribute to diseases of the autonomic
nervous system. This project proposes to leverage novel genetic and advanced imaging techniques to begin
addressing the long-term goal by combining anatomical (Aim 1), cellular (Aim 2), and molecular (Aim 3)
approaches. Aim 1 will establish a comprehensive, high-resolution map of vagus nerve development in the
context of the whole animal, by utilizing genetic labeling, tissue clearing, and high- resolution microscopy. Aim
2 will elucidate the interplay between enteric neuron migration and vagal afferent outgrowth, by utilizing cutting-
edge mouse genetics tools to selectively manipulate different cell types. Aim 3 will identify molecular
determinants of vagus nerve pathfinding, by combining publicly available data and mouse genetics tools to
label and perturb candidate gene expression in vagal sensory neurons. It is becoming increasingly apparent
that vagus nerve connectivity plays a role in metabolism and energy homeostasis, with implications in
related disorders. Therefore, results of this project will open new lines of inquiry on how viscera-to-brain
communication is established and maintained in health and disease.!

## Key facts

- **NIH application ID:** 9767520
- **Project number:** 5F32DK117798-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Ga Young Lee
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9767520

## Citation

> US National Institutes of Health, RePORTER application 9767520, Molecular pathways underlying organ-specific targeting by the vagus nerve (5F32DK117798-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9767520. Licensed CC0.

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