# Mouse oocyte fate determination via polarized cytoplasmic transport within germline cysts

> **NIH NIH R01** · BUCK INSTITUTE FOR RESEARCH ON AGING · 2021 · $407,400

## Abstract

Abstract:
In adult mammalian females, normal ovarian function is sustained by a pool of primary oocytes that form at the
fetal stage. Massive germ cell apoptosis during primary oocyte formation (i.e., oocyte differentiation) in fetal
ovaries and oocyte development in adult ovaries reduces the oocyte number significantly, leading to limited
reproductive life-span in females. Unveiling the mechanisms of oocyte differentiation, in particular the germ cell
loss during this process is critically important for understanding normal ovarian biology and the pathological
causes of ovarian health issues. The germ cell loss has been attributed to defective germ cells, however, my
recent study in mice suggested a novel role for germ cell loss in oocyte differentiation via a “nursing” process. I
identified germline cysts (interconnected sister fetal germ cells derived from one progenitor) as functional units
for oocyte differentiation. 20% of the fetal germ cells actively collect cytoplasm from the remaining germ cells via
intercellular bridges. The collectors differentiate into primary oocytes, while the donors undergo apoptosis. In
this proposal, we aim to investigate: 1) How the germ cell fates of collecting vs. donating cytoplasm are
determined, and 2) What is the biological significance of cytoplasmic collection in oocyte production. Our
preliminary data show that mouse germline cysts develop as a branched structure, in which ~17% of the germ
cells are connected with three or four intercellular bridges. Germ cells with a higher number (i.e., three or four)
of bridges are preferentially protected from apoptosis, suggesting that the geometry of the cyst impacts germ
cell fates within it. Our ex vivo functional assay revealed that pharmacological inhibition of microtubule
polymerization or dynein motor function blocks cytoplasmic transport, leading to the formation of defective
primary oocytes that fail to develop into mature oocytes. Based on these preliminary data, I hypothesize that
within the cyst, germ cells with a higher number of bridges collect cytoplasm via microtubule-dependent
directional transport to differentiate into primary oocytes; and that cytoplasmic transport through fetal germ cell
connectivity plays an essential role in forming primary oocytes with proper developmental potential in adult
ovaries. We will characterize the pattern of germ cell loss and cytoplasmic transport in the cyst by live-imaging
individual cysts; and investigate how cysts establish polarity that guides cytoplasmic transport by examining
cytoskeletal protein distribution with respect to the cyst geometry. To elucidate the biological significance of fetal
germ cell connectivity, we will examine oocyte differentiation and development in the mouse models, in which
germ cell connectivity is compromised (Tex14 and RacGap mutants). Preliminary results show that fetal germ
cells form abnormal syncytia in Tex14 mutant ovaries owing to a defect in forming stable intercellular ...

## Key facts

- **NIH application ID:** 10113642
- **Project number:** 5R01GM126028-04
- **Recipient organization:** BUCK INSTITUTE FOR RESEARCH ON AGING
- **Principal Investigator:** Christopher Benz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $407,400
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113642

## Citation

> US National Institutes of Health, RePORTER application 10113642, Mouse oocyte fate determination via polarized cytoplasmic transport within germline cysts (5R01GM126028-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10113642. Licensed CC0.

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