# Shared mechanisms regulate transcription-factor activity to control cell fate in neural stem cells and the embryo

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $334,525

## Abstract

ABSTRACT
Development requires that cells robustly exit one cell fate and enter another. In the early embryo the specified
germ cells must be rapidly reprogrammed to the pluripotent cells that can subsequently generate an entirely
new organism. Conversely, following asymmetric stem-cell division the two daughter cells must adopt different
fates with one regenerating the stem cell and the other exiting the multipotent state and initiating differentiation.
These essential developmental transitions require that the activity of those factors that drive pluripotency be
precisely controlled as both too many and too few stem cells are detrimental to the organism. While the
transcription factors that drive stem-cell fate have been well characterized in culture, less is known about how
the activity of these factors is tightly controlled within the context of a developing organism. Our preliminary
data demonstrate a shared role for the transcription factor Zelda (ZLD) as a master regulator of the mulitpotent
state in both the early embryo and larval neural stem cells of Drosophila melanogaster. We have recently
demonstrated that in both the embryo and the larva ZLD can reprogram cells to a multipotent fate and
increased ZLD activity is deleterious. Thus, ZLD activity must be tightly controlled to allow for development to
proceed. Our preliminary data suggest that chromatin structure may limit the ability of ZLD to engage the
genome and reprogram cell fate. ZLD activity is additionally regulated by post-transcriptional mechanisms that
control ZLD levels. Based on these preliminary data we are well positioned to elucidate general mechanisms
by which the activities of master regulators of stem-cell fate are precisely controlled to maintain a balance
between self-renewal and differentiation. We will use genetic, genomic, and biochemical strategies to (1)
identify mechanisms by which chromatin structure influences ZLD activity and (2) determine how post-
transcriptional regulation of zld RNA controls ZLD protein levels in both neural stem cells and the early embryo.
Together these results will have important implications for understanding how the balance between the
multipotent and differentiated states are precisely controlled during development.

## Key facts

- **NIH application ID:** 10401953
- **Project number:** 5R01NS111647-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Melissa Harrison
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $334,525
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401953

## Citation

> US National Institutes of Health, RePORTER application 10401953, Shared mechanisms regulate transcription-factor activity to control cell fate in neural stem cells and the embryo (5R01NS111647-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10401953. Licensed CC0.

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