# Regulation of chromosome segregation during oocyte meiosis

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $300,308

## Abstract

Project Summary
 Organisms that reproduce sexually utilize a specialized cell division program called meiosis to reduce their
chromosome number by half to generate haploid gametes. Proper execution of this process is crucial for a
successful pregnancy, since errors in meiotic chromosome segregation result in aneuploidy (incorrect
chromosome number in the embryos), the leading known cause of miscarriages and birth defects in humans.
Meiosis in females is especially error prone and this vulnerability has a profound impact on human health: it is
estimated that 10-25% of human embryos are chromosomally abnormal, and the vast majority of these defects
arise from problems with the female meiotic cells (called oocytes). However, despite the importance of female
meiosis for successful reproduction and human health, surprisingly little is known about the mechanisms that
act to ensure accurate chromosome partitioning in oocytes.
 Oocytes have some special features that necessitate the use of novel cell division mechanisms. Perhaps
most significantly, oocytes lack centrosomes, which define and organize the spindle poles in other cell types;
therefore, spindles in these cells are morphologically distinct. Using C. elegans as a model, we previously
found that acentrosomal oocyte spindles have a surprising organization; chromosomes are ensheathed by
microtubule bundles that run along their sides, making lateral contacts, instead of forming end-on kinetochore
attachments. Moreover, we also defined new mechanisms that facilitate chromosome congression and
segregation on these spindles, driven by movement of chromosomes along these lateral bundles. Therefore,
our work has revealed a new strategy utilized by C. elegans oocytes for controlling chromosome dynamics
during cell division.
 Building on these discoveries, the goals of the proposed work are to: 1) deepen our understanding of
these newly-discovered mechanisms and 2) to shed light on how they are regulated. An important component
of this kinetochore-independent segregation system is a complex of proteins that form a ring structure around
the center of each chromosome pair (the “midbivalent ring”). Our work will therefore delve into the assembly,
disassembly, organization, and functions of this ring complex, to reveal mechanisms essential for chromosome
segregation on acentrosomal spindles. Moreover, we have also recently discovered that a regulatory
mechanism exists in these cells; in the presence of meiotic errors, oocytes delay key events in anaphase
progression, potentially to increase the fidelity of chromosome segregation. Therefore, we will use a
combination of approaches to investigate error regulation in these cells and to expand and refine our models
for chromosome congression and segregation. These approaches will enable us to gain a mechanistic
understanding of oocyte meiosis, an important yet poorly understood form of specialized cell division.

## Key facts

- **NIH application ID:** 10084902
- **Project number:** 5R01GM124354-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** SARAH Marie WIGNALL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,308
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084902

## Citation

> US National Institutes of Health, RePORTER application 10084902, Regulation of chromosome segregation during oocyte meiosis (5R01GM124354-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10084902. Licensed CC0.

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