# Identifying developmental pathways that regulate bilateral growth symmetry

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2021 · $242,250

## Abstract

Abstract
 Growth is a fundamental property of animal development. While research has uncovered many of the
molecular pathways responsible for regulating tissue size, how the activity of those pathways is coordinated
across different organs or tissues to produce the proportion and symmetry we observe in mature tissues
remains a mystery. In this proposal, we generate an experimental model that will serve as a basis for exploring
symmetric growth coordination (SGC) between paired tissues in the fruit fly Drosophila melanogaster, a
genetically tractable developmental model.
 In Drosophila, adult appendages derive from larval tissues called imaginal discs. During larval
development, damaged imaginal discs can regenerate. In previous work, my research group described how
release of the relaxin hormone Dilp8 by regenerating tissues, and the activation of the Dilp8 receptor Lgr3 in
the brain and endocrine tissues, coordinates the growth of regenerating and undamaged tissues to maintain
appropriate adult proportion. Loss of Dilp8/Lgr3 signaling also produces an increased frequency of
spontaneous growth asymmetries in the wings of mutant animals. However, the low penetrance of this
phenotype makes it difficult to examine how SGC is regulated during development.
 To overcome this experimental difficulty, in this proposal we describe a new genetic model to look at
SGC between paired tissues, such as Drosophila wings. Since male and female wings have different growth
rates, bilateral sexual mosaics, or gynandromorphs, allow us to determine whether compensatory growth
pathways are activated in response to growth asymmetries. Using this genetic model, our preliminary data
reveals that there is growth coordination between male and female tissues in gynandromorphs. We also
observe that gynandromorph development is delayed and that both male and female tissues are smaller. Both
of these phenotypes are consistent with the activation of the Dilp8/Lgr3 pathway in gynandromorphs.
Therefore, we propose genetic approaches to test the role of Dilp8/Lgr3 pathway in mediating SGC in
gynandromorphs. Additionally, by developing a fluorescent reporter for identifying larval gynandromorphs, we
will determine the developmental stages where SGC occurs and identify gene expression patterns associated
with slower and faster growing tissues during growth compensation. Developmental growth compensation
during early human development is associated with higher risk of long-term heath complications, including
metabolic and cardiovascular disease. By examining SGC in our model, we hope to gain insights into the
etiology of these compensation-induced disease states to direct clinical research towards new therapies.

## Key facts

- **NIH application ID:** 10131235
- **Project number:** 5R21HD101785-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** ADRIAN J HALME
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $242,250
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131235

## Citation

> US National Institutes of Health, RePORTER application 10131235, Identifying developmental pathways that regulate bilateral growth symmetry (5R21HD101785-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131235. Licensed CC0.

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