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 Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>