Roundworms' egg cells have a backup plan
Study is first to uncover hidden mechanism that keeps cell division on
track

Date:
March 29, 2022
Source:
Northwestern University
Summary:
Researchers discovered a previously unknown mechanism in roundworms
that protects their egg cells from division errors. Uncovering
and understanding this hidden mechanism could ultimately lead to
new strategies for combating infertility in humans.



FULL STORY ==========================================================================
For reproduction to be successful, an egg cell must divide perfectly. Egg
cell divisions are so error-prone, however, that they are the leading
cause of miscarriages and birth defects in humans.


==========================================================================
In a new study, Northwestern University researchers discovered a
previously unknown mechanism in roundworms that protects their egg cells
from division errors. Uncovering and understanding this hidden mechanism
could ultimately lead to new strategies for combatting infertility
in humans.

"Prior to our work, certain proteins were thought to be essential
for cells to divide," said Northwestern's Sadie Wignall, who led the
study. "However, when we removed these proteins, we were surprised to
discover a previously hidden 'backup' mechanism that was able to kick in
when the main proteins were missing. We uncovered something that other researchers missed because, if the major mechanism is in place, then
you wouldn't know that backup existed." The study was published today
(March 29) in the journal eLife.

Wignall is an associate professor of molecular biosciences at
Northwestern's Weinberg College of Arts and Sciences. Gabriel Cavin-Meza,
a graduate student in Wignall's laboratory, is the paper's first author.

When an egg is fertilized with sperm, the resulting embryo begins to
rapidly divide, eventually developing into a healthy organism. If either
the egg or the sperm have the wrong amount of genetic material, however,
then the organism cannot properly develop.



========================================================================== While other cells in the human body divide perfectly more than 99% of the
time, egg cells are mysteriously error prone. About 10-25% of the time,
egg cells incorrectly divide, resulting in the wrong amount of genetic
material ending up in the embryo.

To understand why egg cells are more susceptible to errors, Wignall
studies a football-shaped structure, called the spindle, which organizes genetic material before the egg divides.

"The spindle is like a machine," Wignall said. "It lines up chromosomes
and then pulls them apart, ensuring that the right number of chromosomes
end up in each half of the cell." The spindle is made up of long
ropelike structures called microtubules. The microtubules gather into
points at each pole of the spindle, giving it its football shape. Then microtubules attach to the chromosomes and eventually pull them apart.

"Motor proteins bind to the microtubules and take steps to move along
them - - just like humans walk using their legs," Wignall said. "When microtubules are first formed, they are a random mess. Then the motors
use this walking motion to push the microtubules around to arrange them
into the spindle structure." Before Wignall's new study, researchers
believed two motor proteins (dynein and kinesin-12) were primarily
responsible for this task. But when Cavin-Meza removed both proteins
from roundworms' egg cells, he saw something shocking.



========================================================================== "When we removed these proteins, it made the entire spindle blow apart," Wignall said. "Then we were surprised to see the spindle reform."
In the absence of dynein and kinesin-12, another motor protein (called
kinesin- 5) came out of hiding to perform its backup duty. In the end,
this previously unknown mechanism restored the spindle structure,
allowing the chromosomes to be pulled apart.

Although this study was completed in C. elegans -- a well-studied
roundworm that is commonly used as a model for reproduction -- Wignall
believes similar mechanisms might be present in humans. But because so
few human eggs cells are donated to science, researchers study model
organisms to probe questions and work out details before examining humans.

"All of the components in our study are also present in human eggs,"
Wignall said. "Spindles seem to form the same way in humans and even look exactly the same. It would be really interesting to see if humans also
have this backup mechanism." The study, "Multiple motors cooperate to establish and maintain acentrosomal spindle bipolarity in C. elegans
oocyte meiosis," was supported by the National Institutes of Health
(award numbers R01GM124354 and T32 CA009560).


========================================================================== Story Source: Materials provided by Northwestern_University. Original
written by Amanda Morris. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Gabriel Cavin-Meza, Michelle M Kwan, Sarah M Wignall. Multiple
motors
cooperate to establish and maintain acentrosomal spindle bipolarity
in C.

elegans oocyte meiosis. eLife, 2022; 11 DOI: 10.7554/eLife.72872 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220329142538.htm

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