# Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis

> **NIH NIH R35** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $81,929

## Abstract

Project Summary
Meiosis is the cell division process that is essential for sexual reproduction because it creates haploid gametes
from diploid precursor cells. Chromosome segregation during meiosis I (MI) is unique because replicated sister
chromatids remain attached to one another while homologous chromosome pairs segregate. In humans,
mistakes in MI occur are strikingly high in female gametes (oocytes), resulting in infertility, miscarriage, or birth
defects, yet the molecular mechanisms that control MI are poorly understood. Work in our lab has been
instrumental in dissecting the signaling mechanisms used to control MI to explain this phenomenon.
The Aurora protein kinase family is comprised of three members: AURKA, AURKB and AURKC. The AURKs
are essential regulators of chromosome segregation in mitosis, and their activities are required for completing
MI chromosome segregation. AURKC expression is limited to gametes and is aberrantly expressed in some
cancers. Yet, because AURKC shares high sequence homology with AURKB standard approaches to
understand their MI-specific functions were not sufficient. Our expertise in creating and evaluating oocyte-
specific AURK knockout mice has afforded us the ability to unravel the mystery of why oocytes contain two
kinases that are similar to one another. Not only have we identified AURKB and AURKC functions that are
distinct from one another, we have discovered that the three AURKs regulate one another. In this proposal, we
aim to continue to dissect the requirements for each AURK during MI, and to determine how and why the
AURKs regulate one another. By studying the functions of all three AURK family members, we will uncover the
evolutionary benefit and the consequences of expressing three AURKs. To do so we will: 1) Elucidate how
AURKA and AURKC counter-acting activities are required to build an MI spindle, 2) examine cell lines that
aberrantly express AURKC to determine if these counter-acting activities drive aneuploidy in mitosis, and 3)
determine how AURKB regulates proteins required for the spindle assembly checkpoint during MI.
Information gained from our studies will help us fully understand how these kinases operate during MI while
highlighting distinct differences between how mitosis and MI are controlled. Importantly, these data will shed
light on how MI chromosome segregation is controlled in oocytes and why it commonly goes awry in women
leading to aneuploidy.

## Key facts

- **NIH application ID:** 10455188
- **Project number:** 3R35GM136340-02S2
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Karen A Schindler
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $81,929
- **Award type:** 3
- **Project period:** 2020-09-17 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455188

## Citation

> US National Institutes of Health, RePORTER application 10455188, Signaling Mechanisms that Control Chromosome Segregation during Female Meiosis (3R35GM136340-02S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455188. Licensed CC0.

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