# Regulation of stem cell differentiation during Drosophila oogenesis

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT ALBANY · 2021 · $64,844

## Abstract

Abstract
The production of gametes is pivotal to launching the next generation. To generate gametes, germline stem cells
(GSCs) must exit the mitotic program, which governs self-renewal and transit amplification, and initiate the
meiotic program. While several germ cell intrinsic mechanisms that repress the meiotic program during the
mitotic phase have been described, little is known about how the mitotic program is regulated. We have
identified a specialized transcriptional complex that permits the expression of a germline-specific
ribosomal protein that regulates the mitotic program and the shift to meiosis. We discovered an
unexpected role for the conserved Male-specific lethal 3 (Msl3) protein in regulating female germline mitotic
phase transcription. In Drosophila, Msl3 is part of the Dosage Compensation Complex (DCC) that upregulates
transcription from the X chromosome in males. We find that msl3 is expressed in the mitotic phase of the female
germ line, where it acts independently of the DCC to both promote GSC maintenance and transition into meiotic
fate. Our data suggest that Msl3 recruits the histone acetyltransferase (HAT) activity of the Ada2a-Containing
(ATAC) complex. We found that loss of msl3 and ATAC complex components lead to reduced transcription of a
ribosomal protein, RpS19b. We find that RpS19b is expressed specifically in the germline mitotic stages and
propose that it controls translation of factors such as RNA binding protein Fox 1 (Rbfox1) to regulate the mitosis-
to-meiosis switch. The objective of this proposal is to uncover how Msl3 regulates the transition from the mitotic-
to-meiotic program via RpS19b. Our central hypothesis is that Msl3 recruits HAT activity via the ATAC complex
to promote transcription of RpS19b, which in turn regulates Rbfox1 translation. We plan to test our hypothesis
with the following three specific aims: 1) Determine how Msl3 promotes oogenesis. 2) Determine the role of
HATs in Msl3-dependent transcription. 3) Uncover the role and mechanism of RpS19b in oogenesis. The
rationale for the proposed work is that insight into Msl3-mediated regulation of the mitotic-to-meiotic transition
will illuminate how functional oocytes are generated. In mammals, Msl3 is part of the Male Specific Lethal (MSL)
complex, which regulates maintenance and differentiation from the pluripotency program, suggesting a potential
conserved function of Msl3 in stem cell compartments.

## Key facts

- **NIH application ID:** 10256640
- **Project number:** 5R01GM111779-08
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT ALBANY
- **Principal Investigator:** Prashanth Rangan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $64,844
- **Award type:** 5
- **Project period:** 2014-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256640

## Citation

> US National Institutes of Health, RePORTER application 10256640, Regulation of stem cell differentiation during Drosophila oogenesis (5R01GM111779-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10256640. Licensed CC0.

---

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