# Oocyte development in Drosophila

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $662,808

## Abstract

Summary
 The goal of this project is to investigate a special type of intercellular communication common in animal
germline cells. From flies to humans, the development of eggs and sperm is carried out in groups of germline
cells connected by intercellular bridges that allow the exchange of cytoplasm. Disruption of intercellular
exchange causes infertility. These intercellular bridges, called ring canals, arise from mitotic cleavage furrows
between cells that do not complete cytokinesis. Ring canals are also present in several somatic epithelial
tissues in the fruit fly Drosophila, providing evidence that stable intercellular bridges are relevant to non-
germline biology. The experiments are designed to elucidate the composition, regulation and function of ring
canals using the powerful genetic and cell biological approaches in the Drosophila model system. The three
integrated aims of this proposal will greatly enhance the understanding of ring canal formation and regulation,
identify new ring canal components, and examine the function of ring canals in the male germline and somatic
tissues.
 Research proposed in Aim 1 will investigate the regulation of the actin cytoskeleton of female germline ring
canals, which is responsible for the expansion of ring canals that is needed to accommodate movement of
maternal cytoplasm to the growing oocyte. Recent work in the lab uncovered an unusual regulatory
mechanism for controlling the organization of filamentous actin that involves protein degradation via the
ubiquitin proteasome system and the activity of an E3 ubiquitin ligase. Proteomic and biochemical approaches
will be used to identify substrates of the ligase and characterize their role in F-actin assembly at the ring canal.
Since the E3 ubiquitin ligase involved with organizing ring canal F-actin is highly conserved, these experiments
will be of great interest to researchers studying regulated protein degradation. Experiments in Aim 2 will
quantify the largely uncharacterized cytoplasmic exchange occurring in both germline and somatic ring canals
in the male reproductive tract. To elucidate the functional importance of ring canals, novel strategies involving
targeted destruction or occlusion of ring canals will be carried out. The results will reveal the importance of
communication and molecular exchange through ring canals in these tissues. Newly optimized proteomic
methods proposed in Aim 3 involve in vivo chemical labeling with a biotin tag and extraction of intact ring
canals or ring canal components. The proteomes of germline and somatic ring canals in male and female
reproductive tissues will be compared, allowing new insight into their composition and the conserved features
of ring canals. The comparative proteomics approach will also reveal new ring canal constituents to target for
genetic and functional analysis. Another approach will use the same tools to probe localized protein
environments, rather than overall composition, and will yiel...

## Key facts

- **NIH application ID:** 9851399
- **Project number:** 5R01GM043301-29
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Lynn COOLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $662,808
- **Award type:** 5
- **Project period:** 1990-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851399

## Citation

> US National Institutes of Health, RePORTER application 9851399, Oocyte development in Drosophila (5R01GM043301-29). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851399. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
