Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cannibalistic signals help mammalian embryos develop normally

30.08.2007
A cannibalistic process called autophagy spurs dying embryonic stem cells to send "eat me" and "come get me" signals to have their corpses purged, a last gasp that paves the way for normal mammalian development, UT Southwestern Medical Center researchers have found.

Autophagy is the way cells devour their own unwanted or damaged parts. It was known to be active in cell death that occurs during normal embryonic development, but its precise role was unclear.

Some thought it might contribute to cell death or actually help keep cells alive.

The novel role autophagy plays in removing cells that die during normal embryonic development is described in a study appearing online today in Cell. Mouse embryos lacking autophagy have cells that can't make the chemical signals needed for their removal by healthy cells. If dead cells build up, it can result in abnormal development and inflammation and also trigger autoimmune disease.

"The activation of autophagy in cells destined to die may serve to clear dead cells and prevent detrimental inflammation during normal development or when cell death occurs in certain diseases," said Dr. Beth Levine, professor of internal medicine and microbiology and chief of the division of infectious diseases at UT Southwestern. "Our findings also suggest that defects in autophagy might trigger autoimmune diseases and, if so, reversing the defects could potentially help treat such diseases."

To determine autophagy's role in development, Dr. Levine, the Cell study's senior author, and her research team examined autophagy in mouse embryonic stem cells during cavitation. In this earliest wave of programmed cell death that occurs during mammalian development, cells form a ball, known as an embryonic body, and cells in the center die and are removed, leaving a gap.

But in mouse embryonic bodies lacking the autophagy genes atg5 or beclin1, cells died normally but remained in the center. The embryonic bodies then failed to develop normally.

Researchers took this a step further and studied actual mice that lacked the autophagy genes in their lung and retinal tissues, finding that healthy cells engulfed fewer than 25 percent of dead cells during embryonic development, compared to 75 percent in normal mice.

"Without autophagy, the dead cells just don't get engulfed very efficiently," Dr. Levine said. "If you don't have rapid removal of dead cells, you get a lot of unwanted inflammation."

But why do the dead cells in normal embryos disappear?

Through the study, Dr. Levine and the researchers demonstrated it is due to autophagy's ability in dying cells to prompt signals for engulfment by healthy cells. Engulfment depends on signals from the dying cells. An "eat me" signal is made when the chemical phosphatidylserine is exposed on the outside of cell's membrane. A "come get me" signal is made through the secretion of another chemical, lysophosphatidylcholine.

The autophagy-deficient mouse embryonic bodies failed to develop normally because their cells didn't expose phosphatidylserine and secreted low levels of lysophosphatidylcholine, the study shows.

"In other words, they didn't generate either of these two needed signals," Dr. Levine said.

The researchers also found that the cells of the autophagy-deficient mouse embryos had low levels of ATP, a vital energy source for many cellular functions. Autophagy is known to generate amino and fatty acids utilized in ATP production.

Treatment with an alternative fuel, methylpyruvate, restored normal levels of ATP in autophagy-deficient mouse embryonic bodies and bypassed the bodies' failure to prompt signals needed for the healthy cells to engulf the dead ones, Dr. Levine said.

"This study shows that autophagy-induced signals are essential for normal development," she said. "It also raises the possibility that defects in autophagy might spur inflammation in human conditions with cell death, such as neurodegenerative diseases or chemotherapy-treatment of cancer."

Cliff Despres | EurekAlert!
Further information:
http://www.utsouthwestern.edu
http://www.utsouthwestern.edu/home/news/index.html

Further reports about: Development Embryonic Levine autophagy healthy cells inflammation mammalian mouse embryo

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>