The consequences of mating at the molecular level
Novel mechanism by which mating affects the behavior of germline stem
cells

Date:
October 21, 2020
Source:
University of Tsukuba
Summary:
Researchers identified a novel mechanism by which mating affects
the behavior of germline stem cells (GSCs). By studying Drosophila
melanogaster, the researchers showed that the neurons that are
activated during mating result in increased intracellular calcium
signaling in cells adjacent to GSCs, which in turn resulted in
the activation of the protein matrix metalloproteinase to increase
GSCs. This study describes how stem cell behavior is regulated by
environmental cues.



FULL STORY ========================================================================== While it is known that stem cells have the ability to develop into
all tissues in a precisely regulated process, the way environmental
cues affect stem cell behavior has remained poorly understood. In a
new study, researchers from the University of Tsukuba discovered that
neurons producing the neurotransmitter octopamine regulate the behavior
of germline stem cells (GSCs) in response to environmental cues, such
as mating.


==========================================================================
The ovaries of the fruit fly Drosophila melanogaster have been a robust
model system for studying the relationship between environmental cues and
stem cell biology. In fruit flies, GSCs give rise to eggs and exist in
close proximity to somatic cells. Somatic cells comprise several types
of cells in support of the budding eggs. As with other stem cells,
when GSCs divide, one daughter cell retains its stem cell identity,
while the other differentiates into multiple progeny cells. The balance
between self-renewal and differentiation is tightly regulated, both
by cues within and outside the environment in which GSCs reside (also
called a niche). Mating is one such external cue known to increase GSCs.

"It is well known that a molecule called sex peptide from the male
seminal fluid activates neurons located in the uterine lumen. We have previously shown that these neurons are essential for stimulating
the biosynthesis of ovarian steroid hormones to increase the number
of GSCs," says corresponding author of the study Professor Ryusuke
Niwa. "The goal of our study was to investigate how the information from
mating is transmitted from these neurons to GSCs at the molecular and
cellular levels." To achieve their goal, the researchers took a genetic approach to investigate which gene is responsible for the increase of
GSCs upon mating, and found that the octopamine receptor Oamb is the one through which octopamine exerts its effect on GSCs. Through a series
of experiments, the researchers then found that Oamb in escort cells,
one type of somatic cell adjacent to GSCs, modulates GSC increase after
mating and the subsequent release of octopamine by neurons.

At the molecular level, Oamb activation by octopamine resulted in an
increase in calcium signaling in escort cells. Calcium is a potent
biomolecule and changes in cellular calcium levels strongly affect
cell behavior.

Because it had previously been shown that ovarian steroid hormones were involved in the increase of GSCs, the researchers next investigated the relationship between ovarian steroid hormones and the calcium-dependent
GSC increase. Their results showed that ovarian steroid hormones are
indeed required to increase the number of GSCs. Next, the researchers
asked which molecules play a role in stimulation of escort cells
by octopamine and found that the protein matrix metalloproteinase
2 is required upon the calcium- dependent GSC increase. Finally, the researchers showed that the neurons projecting to the ovaries to increase
GSCs do so via specialized proteins, called nicotinic acetylcholine
receptors. These results provide a complete picture as to how neuronal activation results in increased ovarian stem cells.

"These are striking results that show the molecular mechanism underlying
the coupling of the nervous system with stem cell behavior in response to environmental cues, such as mating," says Professor Niwa. "Our results
could help unravel the conserved systemic and neuronal regulatory
mechanisms for stem cell homeostasis in animals."

========================================================================== Story Source: Materials provided by University_of_Tsukuba. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Yuto Yoshinari, Tomotsune Ameku, Shu Kondo, Hiromu Tanimoto,
Takayuki
Kuraishi, Yuko Shimada-Niwa, Ryusuke Niwa. Neuronal octopamine
signaling regulates mating-induced germline stem cell increase
in female Drosophila melanogaster. eLife, 2020; 9 DOI:
10.7554/eLife.57101 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201021112404.htm

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