# Elucidating the cytoskeletal mechanics in stem cell niche morphogenesis

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $46,752

## Abstract

Project Abstract:
Defects in stem cell function severely impact human health by inducing tumor formation or tissue degeneration.
To maintain a proper balance of self-renewal and differentiation, stem cells rely on signaling cues from their
niche, which is the microenvironment in which they reside. It is imperative to understand the intricacies that
underlie niche biology to reveal mechanisms that promote normal stem cell function and minimize defects in
human health. In many tissues, the niche has a precise and reproducible morphology. However, not much is
known about how niche morphology is controlled or how it impacts niche function. This project will use the
Drosophila gonad to study the mechanics of niche formation, combining genetic tractability with powerful live-
imaging techniques pioneered in the DiNardo lab. In this system, the niche has a distinct morphology defined
by a smoothened boundary between the niche and the adjacent stem cells. This boundary is further referred to
as the niche periphery. Functionally, the niche plays key roles in regulating stem cell behavior: 1) it is the
source for self-renewal cues, 2) it restricts access of these cues to only adjacent cells, and 3) it regulates stem
cell division orientation. Preliminary evidence suggests that the smooth niche periphery is crucial to ensure
proper division angles for germline stem cells (GSCs), suggesting a link between niche structure and function.
Furthermore, F-actin and Myosin II (MyoII) are enriched at the niche periphery, accompanied by tensile forces,
suggestive of actomyosin contractility. A key goal for this project is to unveil the role of actomyosin contractility
in niche morphogenesis and function (Aim 1). Since niche morphogenesis is highly reproducible, this project
will also address upstream mechanisms that robustly polarize F-actin and MyoII to the niche periphery (Aim 2).
An intriguing possibility is that mechanical forces exerted on the niche by adherent GSCs induce cytoskeletal
polarization along the niche periphery. Preliminary evidence suggests GSC divisions are required for proper
niche morphology, and it is known that multiple forces act in concert to drive spindle elongation in a dividing
cell. This project will address the Hypothesis that F-actin and MyoII enrichment along the niche periphery is
induced by GSC spindle elongation, and is necessary for niche formation and function. A combination of
transgenic techniques will be used to manipulate actomyosin contractility, as well as inhibit microtubule motors
involved in spindle elongation. This project will potentially unveil a feedback mechanism where stem cells
shape the niche that guides their behavior, and will be among the first to describe the mechanisms of shaping
a functional niche. The training plan for this project consists of lab work, conference attendance, journal clubs,
lab meetings, graduate group seminars, and exposure to teaching and mentoring roles. This work will be
completed unde...

## Key facts

- **NIH application ID:** 10386101
- **Project number:** 1F31HD105342-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Bailey Nicole Warder
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386101

## Citation

> US National Institutes of Health, RePORTER application 10386101, Elucidating the cytoskeletal mechanics in stem cell niche morphogenesis (1F31HD105342-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10386101. Licensed CC0.

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