# Gene regulatory mechanisms required for neuronal chemosensitivity

> **NIH NIH F30** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $51,036

## Abstract

PROJECT SUMMARY / ABSTRACT:
Chemosensitive areas of the mammalian brainstem regulate breathing and are stimulated by small increases in
carbon dioxide (CO2) levels in arterial blood. The genetic and molecular bases for this chemosensitivity are poorly
understood. C. elegans is an excellent genetic model for probing this question because it possesses CO2-sensitive
neurons - the BAG neurons - that mediate stereotyped behavior and whose cell physiology can be studied in vivo.
BAG cell fate is determined by ETS-5, an ETS-domain transcription factor. Strikingly, the mammalian homolog
of ETS-5, Pet1, is required for the development of CO2-chemosensitive brain regions, and Pet1 mutants have
defects regulating breathing in response to CO2 challenges. To find molecules important in CO2 sensing in C.
elegans and perhaps in vertebrates, I analyzed the direct transcriptional targets of ETS-5 using ChIP-seq. Then, to
clarify which of these targets are being directly regulated by ETS-5 in BAG, I performed mRNA-seq on wild type
versus ets-5 mutant BAG neurons. To determine which of these targets are functionally important for CO2
sensing, I performed a behavioral screen for CO2 avoidance defects. RGS-6 is a G-protein activating protein that is a
direct ETS-5 transcriptional target that appears to be down-regulated in an ets-5 mutant background, and rgs-6
mutation also results in an avoidance defect. To better understand the role of RGS-6 in CO2 sensing, I will (1)
determine the expression pattern, site, and time of action of rgs-6 in CO2 sensing, (2) place RGS-6 in a GPCR
pathway, and (3) determine the physiological role of RGS-6 in CO2 sensing. The proposed studies will integrate
molecular genetics, genomics, and in vivo functional imaging to elucidate the role of a novel RGS protein in CO2
sensing. Because Pet1-like factors are conserved between C. elegans and humans, our studies will likely elucidate
mechanisms required for the function of chemosensitive neurons in the brain, which play critical roles in regulating
breathing and whose dysfunction is linked to fatal apneas.

## Key facts

- **NIH application ID:** 10122752
- **Project number:** 5F30HD094483-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Mary Grace Rossillo
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-03-13 → 2022-03-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122752

## Citation

> US National Institutes of Health, RePORTER application 10122752, Gene regulatory mechanisms required for neuronal chemosensitivity (5F30HD094483-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122752. Licensed CC0.

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