# Regulation of Germ cell to maternal transition

> **NIH NIH R35** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $594,133

## Abstract

Abstract
The gametes arise either from germ cells or germline stem cells (GSCs), by undergoing differentiation and
meiosis. The gametes help launch the next generation by sustaining early development prior to zygotic
genome activation by contributing specific components to the zygote. In particular, the mature oocyte, in
addition to a haploid genome, contains a “maternal contribution” of RNAs, proteins, complexes, and
organelles that is critical to establish a totipotent zygote. Moreover, the oocyte cytoplasm is also sufficient to
reprogram a quiescent somatic cell nucleus to totipotency. Thus, the oocyte's maternal contribution is
essential and critical for totipotency. Germ cells undergoing differentiation and meiosis to eventually
synthesize maternal contribution is conserved up to human. Nevertheless, the mechanisms that establish this
highly potent oocyte cytoplasm during oogenesis are incompletely understood. Using Drosophila as a model
system, my lab has discovered a germ cell-to-maternal transition, wherein germ cell-specific programs,
such as those that promote GSC self-renewal, differentiation, and entry into meiotic cell cycle, are silenced
once the oocyte is specified. Our work reveals that this silencing of the germ cell program is critical to
establishing the “correct” maternal contribution by excluding transcripts that could interfere with development
of the early embryo. We find that this silencing is is mediated by heterochromatin formation to and removal of
perduring RNAs by RNA degradation pathways. Although, we are beginning to understand how germ cell
specific programs are silenced during the germ cell-to-maternal transition several aspects remain poorly
characterized. The objective of the proposal is to uncover how the germ cell-to-maternal transition is
regulated by addressing the following questions: 1. How do the changes in gene expression during the germ
cell-to-maternal transition relate to reorganization of the genome?, 2. How are germ cell-specific genes
targeted for silencing? and 3. How is silencing of germ cell-specific genes coordinated with oocyte
specification? The rationale for the proposed work identifying regulators of this transition and the underlying
molecular mechanisms could reveal new etiologies and therapies for human infertility and novel concepts in
developmental biology.

## Key facts

- **NIH application ID:** 10765423
- **Project number:** 1R35GM152236-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Prashanth Rangan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $594,133
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765423

## Citation

> US National Institutes of Health, RePORTER application 10765423, Regulation of Germ cell to maternal transition (1R35GM152236-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10765423. Licensed CC0.

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