# Morphogen control of organ growth in Drosophila

> **NIH NIH R35** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $58,715

## Abstract

Project Summary
The main goal of this grant is to determine how morphogens control organ growth during animal development.
Morphogens are secreted signaling molecules that spread through developing tissues and control gene
expression, pattern, polarity and growth. The major superfamilies of morphogens are conserved in all
multicellular animals, from sponges to man. Understanding how they work has enormous implications for
human health, as genetic and environmental perturbations of their activities and signal transduction pathways
cause diverse developmental and physiological disorders as well as a wide range of cancers. Research on
morphogens is thus critical for developing diagnostic and therapeutic tools to treat human disease, a central
mission of the NIH.
 Our past studies, using Drosophila, were instrumental in establishing that members of three
superfamilies of secreted proteins, Wingless/Ints (Wnts), Bone Morphogenetic Proteins (BMPs) and
Hedgehogs (Hhs) all function as bona fide morphogens. Initially these studies were focused on determining
both the logic and molecular mechanisms by which these molecules control gene expression, pattern and
polarity. Here, we turn to the fundamental and enduring mystery of how they organize growth.
In the proposed research, we will test and extend a new model we have posited for growth based on our recent
discoveries about how Drosophila Wingless (Wg), a founding member of the Wnt superfamily, controls the
dramatic expansion of the developing wing, a classic paradigm for morphogen action. In this model, Wg and a
second morphogen Decapentaplegic (Dpp), a BMP, act together to sustain the growth of wing cells and to
recruit new cells into the wing primordium by regulating expression of the selector gene, vestigial (vg), a
transcription factor that defines the “wing” state. We have evidence that the key events in this process are
mediated by a single enhancer element in the vg gene, which integrates Wg and Dpp input, as well as a third
“recruitment” signal that depends on transient activation of the conserved Warts-Hippo tumor suppressor
pathway and its transcriptional effector Yorki (Yki, a YAP). We will combine genetic, transgenic and molecular
approaches to establish the roles of all three signaling systems, as well as the molecular mechanism(s) by
which they are integrated by this enhancer. We will also seek to clarify how Wg and Dpp move through tissue
to achieve the appropriate range, and to determine the mechanism(s) responsible for terminating growth when
the wing reaches the correct size. Finally, we will ask if the principles we elucidate in the wing can be
generalized to other organ systems in the fly.

## Key facts

- **NIH application ID:** 10402173
- **Project number:** 3R35GM127141-04S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Gary Struhl
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $58,715
- **Award type:** 3
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402173

## Citation

> US National Institutes of Health, RePORTER application 10402173, Morphogen control of organ growth in Drosophila (3R35GM127141-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10402173. Licensed CC0.

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