Scientists at the Medical Research Council's National Institute
for Medical Research (NIMR; now part of the Francis Crick
Institute) have identified a protein called Schnurri that
protects some epithelial cells against apoptosis, or cell suicide,
in fruit flies.
The protein is also found in humans and so the research has
implications for many diseases that are caused by a failure to
eliminate defective cells, such as cancer.
Dr Jean-Paul Vincent of NIMR explained: "Most tissues are made
of epithelia, sheets of cells that adhere to each other. Epithelial
cells line the surfaces and cavities of our bodies - such as our
skin and glands. When cells become detached from these sheets, they
activate a stress pathway called JNK that leads to their
elimination by apoptosis, a type of ordered cell suicide.
"The same stress pathway is required for epithelial cells to
undergo migration, for example during the movement that brings two
epithelia together in an embryo and allows it to develop its shape.
In developmentally programmed situations like this, the JNK pathway
does not lead to cell death. This suggests that there is a
protective mechanism at work."
In their current study, the researchers showed that, in the
fruit fly embryo, this protective mechanism involves a protein
called Schnurri, which is also found in humans.
The NIMR researchers worked with colleagues from the University
of Freiburg and the European Laboratory of Molecular Biology in
Heidelberg, both in Germany. The team used a combination of genetic
and molecular techniques to decipher the regulation of reaper, a
key gene involved in cell death in the fruit fly. They then studied
mutant fruit flies lacking the Schnurri protein and, using
cutting-edge 3D imaging, found that cells at the edge of migrating
epithelial layers undergo excessive cell death.
Dr Vincent said: "Since Schnurri is present in humans, our
findings could be relevant to many diseases that are caused by a
failure to eliminate defective cells, including cancer. It is
conceivable for example that excessive activity of Schnurri might
protect cells that should otherwise die."
"As a first step to address this possibility, it will be
important to determine whether Schnurri also plays a pro-survival
role in mice. Our study illustrates how organisms such as the fruit
fly that are simple and relatively easily manipulated genetically
can be used to decipher complex gene interactions and thus pave the
way for targeted investigation in higher organisms."
The paper, The Dpp/TGFb-Dependent Corepressor Schnurri Protects Epithelial
Cells from JNK-Induced Apoptosis in Drosophila Embryos, is
published in Developmental Cell.