# Regulation of tubulogenesis in the Drosophila ovary

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $360,337

## Abstract

Project Summary
 The goal of this project is to understand the mechanisms that control tube formation. Tube formation,
the folding of flat epithelial sheets into curved structures, is a basic process in the development of organs such
as the lungs, kidneys, heart, neural tube, and gut. The most common permanently disabling birth defects in
the U.S. result from errors in the development of tubes.
 For several decades, we have studied tube formation in developing egg chambers of the fruit fly,
Drosophila melanogaster. In the fly ovary, flat patches of cells (subsets of the follicular epithelium surrounding
the oocyte) produce a pair of elongated tubes; these tubes synthesize eggshell structures that facilitate gas
exchange in the embryo. Our analyses of wild-type flies demonstrate that tube development in the egg
chamber is remarkably similar to mammalian neural tube formation, the process that creates the spinal chord.
 This proposal capitalizes on and continues our previous studies exploring the molecular, cellular, and
tissue-level factors that contribute to aberrant tube formation in mutants with open, stunted, or branched tubes.
Here we focus on a novel class of growth factors that, when up-regulated, induce aberrant cell migration,
thereby creating open tubes. These "growth" factors, called Imaginal disc growth factors (Idgfs), are related to
human chitinase-like proteins (CLPs), which have poorly understood roles in remodeling tissue and are up-
regulated in autoimmune disorders and metastasizing tumors. We will investigate this gene family in flies by
characterizing the phenotypes of the sextuple knock-out strain. Although most flies die, escapers exhibit
defects in three distinct cell migration processes: germ cell migration in the embryo, abdominal histoblast
migration in the pupa, and dorsal-appendage tube formation in the ovary. We will use genetic, cell biological,
and live-imaging techinques to distinguish between competing hypotheses to explain the underlying molecular
mechanisms for how these factors remodel tissue, focusing our efforts initially on tube formation in the ovary.
Because very little is known about other components that mediate these proteins' activity, we will flesh out the
pathway through a dominant modifer screen followed by functional analysis of the identified interacting genes,
including genes that regulate actin dynamics and planar cell polarity. We will explore the role of the Idgfs and
their network of interacting components by assessing loss-of-function and gain-of-function phenotypes in
another developmental process, that of germ cell migration.
 Since tube formation is highly conserved between invertebrates and vertebrates, and these novel
growth factors are conserved yet poorly understood in any system, our studies will give insight into human
development and disease.

## Key facts

- **NIH application ID:** 10171582
- **Project number:** 5R01GM079433-11
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** CELESTE A. BERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,337
- **Award type:** 5
- **Project period:** 2009-01-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171582

## Citation

> US National Institutes of Health, RePORTER application 10171582, Regulation of tubulogenesis in the Drosophila ovary (5R01GM079433-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171582. Licensed CC0.

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