# Stem cell versus meiotic fate decision in C. elegans

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $399,075

## Abstract

Abstract
 A key point in germ cell development is the switch from stem/progenitor cells to meiosis and
gametogenesis. Disruption of this developmental switch can result in infertility and in some cases germline
tumors. The C. elegans adult hermaphrodite is an important model for understanding control of the switch from
germline stem cell fate to meiotic development/gametogenesis, where a network controlling the process is
emerging. Niche dependent GLP-1 Notch signaling promotes the stem cell fate through repressing three
redundant posttranscriptional pathways that promote meiotic entry: the GLD-1 pathway (which represses
expression of mitotic cycling genes), the GLD-2 pathway (which promotes expression of meiotic genes), and
the SCFPROM-1 pathway that both degrades mitotic cell cycle proteins at meiotic entry and initiates homologous
chromosome pairing. Current studies indicate that while transcriptional programs set the stage, it is largely
posttranscriptional regulation that executes meiotic entry in animals. At a cellular level, we have shown that in
C. elegans the stem cell population is large and germ cells enter meiosis directly, without intervening transit-
amplifying divisions. The absence of transit-amplifying divisions simplifies the analysis allowing straightforward
assays to identify genes involved in repressing meiosis in stem cells and repressing mitotic cell cycling at
meiotic entry and is the primary reason why C. elegans is a major animal model for studying this important
developmental switch.
 This proposal addresses three major gaps in knowledge and a major technical challenge in molecular/
biochemical mechanistic studies of the stem cell/progenitor switch to meiotic development in C. elegans. First,
it is not known how SCFPROM-1 is repressed in stem/progenitor cells. Second, the mRNA targets of the GLD-1
translational repressor and the GLD-2 translational activator, which repress mitotic cycling and promote meiotic
gene product accumulation, are largely unidentified. Third, mechanisms by which GLP-1 signaling is restricted
to the stem cell niche region are not fully known, and the mechanism by which the mett-10 m6A
methyltransferase inhibits GLP-1 signaling is undescribed. Molecular/biochemical studies of the switch from
stem/progenitor cells to meiotic entry are limited by the C. elegans germline containing all stages, present in an
assembly-line order from stem cells to mature gametes, with any given stage a small proportion. We will
develop a genetic system for the synchronous switch from stem cells to meiotic entry, in a sufficiently large
population of germ cells and animals to allow molecular/biochemical studies.

## Key facts

- **NIH application ID:** 10050797
- **Project number:** 2R01GM100756-09
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** TIM SCHEDL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,075
- **Award type:** 2
- **Project period:** 2012-02-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050797

## Citation

> US National Institutes of Health, RePORTER application 10050797, Stem cell versus meiotic fate decision in C. elegans (2R01GM100756-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10050797. Licensed CC0.

---

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