# Understanding the role of the collagen receptor DDR-2 in germ stem cell niche formation

> **NIH NIH F31** · DUKE UNIVERSITY · 2020 · $37,127

## Abstract

Abstract
Germ stem cells self-renew, differentiate, and secure genome transmission to the next generation. Germ stem
cells depend on niches, which are specialized microenvironments that instruct stem cell self-renewal. Niche
extension is a phenomenon in which the niche cells extend elaborate cellular protrusions that surround stem
cells. While niche extension is conserved across organisms, the function and regulators of niche extension
remain unknown. An essential component of niches is the basement membrane. Basement membranes are
secreted, cell-associated, thin sheets of extracellular matrix that structurally support niches, and can regulate
stemness and cell proliferation. Type IV collagen is a major component of basement membranes. Discoidin
domain receptors (DDRs), are a subset of receptor tyrosine kinases that are specifically activated by collagen,
and often signal through mitogen-activated protein kinase (MAPK) cascades. Misregulation of Type IV collagen
and mutations in mammalian DDRs have both been linked to infertility, however, their role in promoting
fecundity is unknown. The Caenorhabditis elegans (C. elegans) germline niche is composed of only a single
cell, the distal tip cell (DTC), which extends long processes that enwrap and maintain germ stem cells by
activating Notch signaling, thus sustaining germ stem cells and fertility. The genetic and visual experimental
tractability of C. elegans allows for rigorous identification of mediators of niche extension and their role in
fertility. Through an expression and DTC-specific RNAi screen, I found that the C. elegans discoidin domain
receptor DDR-2 promotes the formation of type IV collagen aggregates/puncta along DTC niche processes. In
the absence of DDR-2, type IV collagen accumulates internally in the DTC niche and niche process extension
is dramatically reduced. Based on strong preliminary data, my central hypothesis is that DDR-2 and type
IV collagen function in a positive feedback loop to direct the secretion of type IV collagen anchoring
puncta, which drives niche extension and expands the germ stem cell pool. In Aim 1, I will determine
how DDR-2 and type IV collagen interact in the DTC to drive niche extension and germline maintenance
through site of action studies, genetic analysis, live cell imaging of vesicular trafficking, and fertility assays. In
Aim 2, I will determine the downstream effectors of DDR-2 in DTC extension using genetic epistasis analysis
and cell biological studies. Through preliminary findings of a large scale RNAi screen, I will focus on the role of
MAPK/ extracellular signal-regulated kinases (ERK) signaling and vesicular trafficking regulators. Ultimately I
expect my studies will establish a new role for discoidin domain receptor function in germ line niche formation
and fertility, which will help in our understanding and treatment of fertility disorders in humans.
!

## Key facts

- **NIH application ID:** 9863759
- **Project number:** 5F31HD097901-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sara Grace Payne
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,127
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863759

## Citation

> US National Institutes of Health, RePORTER application 9863759, Understanding the role of the collagen receptor DDR-2 in germ stem cell niche formation (5F31HD097901-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9863759. Licensed CC0.

---

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