# Molecular Mechanisms of Respiratory Circuit Connectivity

> **NIH NIH F31** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $40,420

## Abstract

PROJECT SUMMARY/ABSTRACT
 Breathing is an essential motor function for terrestrial life. Developmental and genetic disorders that
disrupt breathing, such as sudden infant death syndrome (SIDS) and Rett syndrome, often have fatal
consequences. This is likely due to the impaired development of neural circuits that control breathing. While
diaphragm muscle contractions, the driving force for inspiration in mammals, are controlled solely by motor
neurons (MNs) located in the phrenic motor column (PMC), respiration is regulated by complex neural circuitry
in the hindbrain. Despite the critical importance of these circuits, the molecular mechanisms that underlie their
connectivity are largely unknown.
 Our lab has shown that Hox5 transcription factors (TFs) drive phrenic MN connectivity and regulate the
expression of phrenic-specific cell adhesion molecules. My preliminary data indicate that Hox5 expression varies
across hindbrain respiratory nuclei, perhaps acting to confer subtype-specific characteristics required for
connectivity. In this proposal, I will investigate the function of Hox5 TFs and their downstream effectors in
establishing respiratory circuit connectivity.
In Aim 1, I will assess how Hox5 gene expression in respiratory premotor neurons underlies specific connectivity
between respiratory populations required for proper circuit function.
In Aim 2, I will use genetic manipulations to determine how select cell adhesion molecules act downstream of
Hox5 TFs to control respiratory connectivity and function.
 I have developed an integrative methodology combining genetic models, RNA-sequencing, retrograde
viral tracing, and electrophysiology to address these questions. Understanding the molecular mechanisms that
underlie respiratory circuit development could lead to improved treatment options for those suffering from
developmental or genetic diseases that affect breathing.

## Key facts

- **NIH application ID:** 10464721
- **Project number:** 1F31NS124240-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Matthew Thomas Moore
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,420
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464721

## Citation

> US National Institutes of Health, RePORTER application 10464721, Molecular Mechanisms of Respiratory Circuit Connectivity (1F31NS124240-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10464721. Licensed CC0.

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