# Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $105,821

## Abstract

Human body temperature increases during wakefulness and decreases during sleep. The
body temperature rhythm (BTR) is a robust output of the circadian clock and is fundamental for maintaining
homeostasis, such as generating metabolic energy and sleep, as well as entraining peripheral clocks in
mammals. However, the mechanisms that regulate BTR are largely unknown. Therefore, there is a crucial need
to identify the molecular mechanisms that regulate BTR.
 Drosophila are ectotherms, and their body temperatures are close to ambient temperature; therefore, flies
select a preferred environmental temperature to set their body temperature. We identified a novel circadian
output, the temperature preference rhythm (TPR), in which the preferred temperature in flies increases during
the day and decreases at night. TPR thereby produces a daily body temperature rhythm. Fly TPR shares many
features with mammalian BTR. During the current grant term, we established that Diuretic hormone 31 receptor
(DH31R), a Drosophila calcitonin receptor family protein, mediates TPR, and we demonstrated that the closest
mouse homolog of DH31R, calcitonin receptor (Calcr), is essential for normal BTR in mice. Importantly, both
TPR and BTR are regulated in a distinct manner from locomotor activity rhythms, and neither DH31R nor Calcr
regulate locomotor activity rhythms. Together, our findings suggest that DH31R/Calcr is an ancient and specific
mediator of BTR. Thus, understanding fly TPR will provide fundamental insights into the molecular and neural
mechanisms that control BTR in mammals.
 The goal of this proposal is to determine the molecular and neural mechanisms of TPR. Our recent study
suggests that DH31 acts on clock neurons via DH31R to regulate TPR. Although DH31 primarily activates
DH31R, DH31 can also activate the Pigment dispersing factor receptor (PDFR), required for locomotor activity
rhythms, at a modest level in vitro. Because PDFR does not play a major role in daytime TPR, we expect that
DH31R and PDFR are expressed in different cells. In addition to the identification of crucial ligand-receptor
interactions, we recently found that master clock cells, the dorsal clock neurons 2 (DN2s), control TPR but not
locomotor activity rhythms. The central hypothesis of this proposal: DN2s have temporally-regulated contacts
with DN1ps and control rhythmic expression of DH31, which activates DH31R in PDFR-negative DN1ps,
resulting in TPR. In Aim 1, we will elucidate the physical and functional relationship between DN1ps and DN2s
to control TPR. In Aim 2, we will determine the mechanism that sets rhythmic DH31 expression in DN1ps. In Aim
3, we will determine the mechanism by which DH31R-expressing neurons control TPR. This project will
contribute to a mechanistic understanding of fly TPR. The outcomes of this study should ultimately provide a
novel mechanistic understanding of the mammalian BTR.

## Key facts

- **NIH application ID:** 10070107
- **Project number:** 5R01GM107582-08
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Tadahiro Goda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $105,821
- **Award type:** 5
- **Project period:** 2013-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070107

## Citation

> US National Institutes of Health, RePORTER application 10070107, Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila (5R01GM107582-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070107. Licensed CC0.

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