# The C. elegans Germline: A Test Tube for Cell and Developmental Biology

> **NIH NIH R35** · UNIVERSITY OF MINNESOTA · 2022 · $254,648

## Abstract

SUMMARY/ABSTRACT
Overview: Reproduction relies on a complex series of cell fate decisions, cell cycle transitions, 
and differentiation events, which coordinate the formation and function of gametes with 
the process of meiosis. A century of research using many experimental organisms, 
including the nematode Caenorhabditis elegans, defined key intercellular signals regulating 
germline development, delineated central players in meiosis, and revealed the importance of 
post-transcriptional gene regulatory mechanisms. Yet, important mechanistic questions remain about 
how intercellular communication integrates the underlying molecular mechanisms into a coherent 
germline developmental program. This research proposal addresses several central questions:
•How do soma-germline gap junctions orchestrate germline development, coordinate 
germline developmental subroutines, and integrate nutritional signals to optimize reproduction?
•How do intercellular signals and gametic interactions regulate protein translation to enable 
fertilization and ensure the vitality of the embryo?
•Can we exploit the dynamic nature of germline development in which germ cell nuclei move within 
the gonadal tube to provide broad insights into the cell biology of diseases affecting the nuclear 
envelope?
Goals: The chief goal of our work is to delineate the regulatory networks governing conserved and 
essential steps in germline development. Our focus will be on three areas: (1) The role of gap 
junctions in controlling soma-germline interactions; (2) The regulation of protein 
translation by intercellular signaling during oocyte meiotic maturation and the 
oocyte-to-embryo transition; and (3) Studies in the C. elegans germline system that provide 
insights into the cell biology of a class of human diseases affecting the nuclear envelope. In 
pursuing these goals, we will fill three key gaps in understanding: (i) the nature of the active 
biomolecules that transit through gap junctions to mediate their many essential reproductive 
functions; (ii) the function and regulation of a large translational regulatory machine that lies 
at the heart of the oocyte meiotic maturation decision and the oocyte-to-embryo transition; and 
(iii) the involvement of nuclear mechanotransduction and endogenous mechanical forces in the 
origin of diseases affecting the nuclear envelope.
Vision: Using the powerful combination of genetic and modern molecular technologies available in C. 
elegans, we will advance our understanding of germline development, germline stem cell behavior, 
and oogenesis. In the course of these investigations, we will discover new molecular principles 
vital to human health and inform the development of novel therapeutic strategies to treat disease. 
This fundamental research in a genetic model system will generate foundational knowledge for 
understanding reproduction and the origin of birth defects.

## Key facts

- **NIH application ID:** 10328427
- **Project number:** 1R35GM144029-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** David Irwin Greenstein
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $254,648
- **Award type:** 1
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328427

## Citation

> US National Institutes of Health, RePORTER application 10328427, The C. elegans Germline: A Test Tube for Cell and Developmental Biology (1R35GM144029-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10328427. Licensed CC0.

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