# Structural and functional coupling of epidermis to somatosensory neurons in Drosophila

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $318,514

## Abstract

Epidermal cells provide the first point of contact for sensory stimuli and are innervated by somatosensory
neurons (SSNs) that shape our experience of the world. Both SSNs and epidermal cells are of great clinical
relevance; SSNs are mediators of physiological and pathological pain, and some pathological skin conditions
are associated with debilitating pain and itch. However, our understanding of roles that epidermal cells play in
SSN development and function, particularly nociception, remain limited aside from a few well-studied
examples. Characterizing these important intercellular interactions is complicated by the heterogeneity and
complexity of vertebrate nervous systems. Drosophila provides an appealing system to close this gap in our
knowledge, offering a wealth of genetic resources, ready imaging access of SSNs/epidermis with single cell
resolution, a compact nervous system, and evolutionary conservation of key regulators of SSN
development/function. In this project we will use an integrated approach to study an evolutionarily conserved
intracellular interaction that involves the wrapping of SSN neurites by epidermal cells. The conservation of this
intercellular interaction and the preferential ensheathment of nociceptors compared to other SSNs suggest that
these sheaths may play key roles in development and function of nociceptive SSNs. Here, we test the
hypothesis that epidermal ensheathment of SSNs functionally couples epidermal cells to SSNs. We will test
this hypothesis using three lines of experimentation. First, we will characterize the response properties of
Drosophila epidermal cells and identify epidermal sensory channels that mediate epidermal responses to
noxious stimuli. Second, we will test requirements for sheaths in epidermal activation of nociceptors, define the
neuronal substrates for epidermally-gated behavior responses, define the SSN repertoire functionally coupled
to epidermal stimulation, and quantify contributions of epidermal activation to sensory-evoked behaviors. Third,
we will identify signaling mechanisms linking epidermis and C4da neurons in the periphery and identify circuit-
level effects of ensheathment. Given the enormous impact of pathological pain on quality of life – chronic pain
affects more Americans than diabetes, heart disease, and cancer combined – understanding how epidermal
cells modulate nociceptive SSN function is of great interest for development of novel therapeutics for pain
management. Successful completion of this project will provide insight into a fundamental component of
somatosensation that represents a novel control point for nociception that could define a new entry point for
pain management.

## Key facts

- **NIH application ID:** 10442736
- **Project number:** 5R01NS076614-11
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Diana Michele Bautista
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $318,514
- **Award type:** 5
- **Project period:** 2011-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442736

## Citation

> US National Institutes of Health, RePORTER application 10442736, Structural and functional coupling of epidermis to somatosensory neurons in Drosophila (5R01NS076614-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10442736. Licensed CC0.

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