# Mechanisms of Asymmetric Cell Division During Female Meiosis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $388,054

## Abstract

Project Summary
During female meiosis, ¾ of the chromosomes are eliminated and only ¼ of the
chromosomes are inherited by a single egg. In contrast, all chromosomes are
distributed among 4 sperm during male meiosis. The elimination of ¾ of the genome to
allow inheritance of only ¼ of the chromosomes is conserved in all animal phyla,
suggesting some fundamental selective advantage. The long-term goals of this project
are to elucidate the molecular mechanisms of chromosome elimination and elucidate the
selective advantages of asymmetric meiotic division. Errors in meiosis lead to the
absence of one chromosome (monosomy) or the presence of an extra chromosome
(trisomy) in 10-30% of human conceptions with the majority of these aneuploidies
leading to embryonic death. By elucidating the mechanisms of meiotic chromosome
elimination in C. elegans, we will identify mechanisms likely to be defective during
human meiosis. Fertilization occurs during female meiosis in nearly all animal species.
Therefore, animals must have mechanisms to prevent incorporation of paternal
chromosomes into the meiotic spindle which could eliminate paternal chromosomes in a
polar body causing lethal monosomy. We have demonstrated that, in C. elegans,
microtubule driven transport moves the meiotic spindle to a cortical position away from
the future site of fertilization, and that the sperm contents are immobilized at the distant
site of fertilization by cortical actin. Cortical positioning of the meiotic spindle and sperm
contents at opposite ends of the zygote resists cytoplasmic streaming which circulates
membranous organelles around the zygote. Actin depolymerization results in
movement of a cohesive unit containing sperm-derived DNA, centrioles, mitochondria
and other membranous organelles with cytoplasmic streaming. However, the resulting
collisions between the sperm contents and meiotic spindle do not result in incorporation
of paternal chromosomes into the meiotic spindle. We seek to elucidate the completely
unexplored mechanism that holds the sperm contents together as a cohesive unit, as
this is both required to allow tethering to cortical actin far from the spindle and, as a
backup mechanism, insulates paternal chromosomes from capture into the meiotic
spindle. We have uncovered a second selective advantage of asymmetric meiosis by
demonstrating that extra chromosomes present in trisomic or triploid C. elegans are
preferentially deposited in a polar body. We seek to determine the mechanisms that
preferentially move extra chromosomes toward the polar body. These mechanisms
allow triploid or aneuploid C. elegans to have a high frequency of offspring with a normal
chromosome number and could be relevant to the health prospects for offspring of
women with triploX syndrome, trisomy 21 or mosaic trisomy. In addition, we will
continue to elucidate the katanin, kinesin and dynein-dependent mechanisms ensuring
bipolar meiotic spindle assembly and positioning. We will accomplish...

## Key facts

- **NIH application ID:** 10133093
- **Project number:** 5R35GM136241-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Francis J McNally
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,054
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133093

## Citation

> US National Institutes of Health, RePORTER application 10133093, Mechanisms of Asymmetric Cell Division During Female Meiosis (5R35GM136241-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133093. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*