# Mechanisms of KIT signaling in the regulation of primordial follicle formation

> **NIH NIH R03** · SYRACUSE UNIVERSITY · 2022 · $74,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Despite its importance to the continuation of species, the differentiation of primordial
germ cells into functional oocytes is poorly understood. Primordial germ cells begin to
differentiate into oocytes during embryonic development in the mouse. The oocytes develop in
clusters called germline cysts, a conserved phase of oocyte development in both vertebrates
and invertebrates. Oocytes progress through prophase I of meiosis and arrest at the diplotene
stage. They then undergo primordial follicle formation during which germ cell cysts break apart
into single oocytes (cyst breakdown) and granulosa cells migrate around individual oocytes to
form primordial follicles. During the process of cyst breakdown, a subset of cells in each cyst die
with only a third of the initial number of oocytes surviving to form primordial follicles. The
mechanisms that control meiotic progression, cyst breakdown, granulosa cell recruitment and
oocyte survival are not well understood. Our long-term goal is to understand molecular and
cellular mechanisms used to establish the primordial follicle pool in the mouse ovary. The
objective of this proposal is to understand the role of the KIT signaling pathway in regulating
meiotic prophase I and primordial follicle formation. The central hypothesis of the proposed
research is that signaling from the receptor tyrosine kinase, KIT, promotes primordial follicle
formation and oocyte progression to the diplotene stage of prophase I through the regulation of
downstream targets. Recent work from our laboratory suggests KIT signaling may play an
important role. This proposal explores the molecular and cellular aspects of KIT signaling in
establishing the pool of primordial follicles. The specific aims of this research are to: 1) elucidate
the role of KIT signal transduction in primordial follicle formation and oocyte progression through
meiotic prophase I; and 2) identify targets downstream of KIT that are important during oocyte
development. These goals will be achieved through techniques including
immunohistochemistry, confocal microscopy, ovary organ culture, real time PCR and single cell
RNA sequencing analysis. Research proposed in the current application is significant because it
will enhance our current knowledge by elucidating the mechanisms important to establish the
primordial follicle pool. Results obtained in this grant will help improve research efforts in
ovarian biology and in treatment of conditions causing female infertility such as primary ovarian
insufficiency.

## Key facts

- **NIH application ID:** 10527518
- **Project number:** 1R03HD102016-01A1
- **Recipient organization:** SYRACUSE UNIVERSITY
- **Principal Investigator:** Melissa E Pepling
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $74,500
- **Award type:** 1
- **Project period:** 2022-08-09 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527518

## Citation

> US National Institutes of Health, RePORTER application 10527518, Mechanisms of KIT signaling in the regulation of primordial follicle formation (1R03HD102016-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10527518. Licensed CC0.

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