# ANALYSIS OF GERM LINE SEX DETERMINATION IN C ELEGANS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1994 · $223,590

## Abstract

Germline development is fundamental to all metazoans and includes four
crucial processes: 1) the decision to enter the meiotic pathway, 2)
progression through meiotic prophase, 3) sex determination, and 4)
gametogenesis.  The proposed research examines germline development in
C elegans through a genetic and molecular study of three genes which
control these processes (gld-1, gld-2, and fog-2).  gld-1 null mutants
have a striking tumorous phenotype (proliferation throughout the
germline), with a novel origin (germ cells that enter the meiotic pathway
fail to progress through meiotic prophase and re-enter the cell cycle).
The gld-1 tumor suppressor locus has multiple roles in germline
development.  It is required not only for progression through meiotic
prophase, but also for male sex determination in the hermaphrodite
germline, and oogenesis.  gld-2, a new locus with a tumorous germline
phenotype, also affects somatic sex determination.  fog-2, like gld-1,
is necessary for male sex determination in the hermaphrodite germline.
Proposed studies of these three interrelated genes provide an important
starting point for our long-term goal of describing germline development
as a molecular-genetic pathway.

Analysis of gld-1:  One major aim is to determine the structure of the
gld-1 products(s), define domains that are necessary for different
germline functions, and examine temporal and spatial patterns of
expression.  The second aim is to determine the role of the somatic gonad
and the glp-1 gene in the tumorous phenotype.  The third aim is to
understand how the multiple functions of gld-1 are coordinated in
germline development by identifying genes that are targets, or that act
to assist or regulate gld-1.

Analysis of gld-2:  To understand the range of processes controlled by
gld-2, a detailed genetic analysis of the locus will be performed.  The
cellular basis of the tumorous phenotype, as well as the roles of the
somatic gonad and the glp-1 gene in tumor formation, will be determined.

Analysis of fog-2:  The structure of the fog-2 product and the temporal
and spatial pattern of expression will be determined.  We have previously
proposed that fog-2 promotes male germline development by negatively
regulating the tra-2 receptor.  Regulation of tra-2 by fog-2 will be
tested genetically and using the yeast two-hybrid system.

The health relatedness of the proposed work is two-fold.  First, research
on germline development in simple, experimentally accessible, metazoan
systems such as C elegans provides fundamental information about
developmental processes in all animals, including humans.  Second, the
gld-1 and gld-2 genes provide a useful in vivo model for germline tumor
formation that may be applicable to human cancer.

## Key facts

- **NIH application ID:** 2199654
- **Project number:** 5R01HD025614-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** TIM SCHEDL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $223,590
- **Award type:** 5
- **Project period:** 1989-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199654

## Citation

> US National Institutes of Health, RePORTER application 2199654, ANALYSIS OF GERM LINE SEX DETERMINATION IN C ELEGANS (5R01HD025614-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199654. Licensed CC0.

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