Controlling body size by regulating the number of cells

August 06, 2003

Why are elephants bigger than mice? The main reason is that mice have fewer cells. Research published in Journal of Biology this week uncovers a key pathway that controls the number of cells in an animal, thereby controlling its size.

Ernst Hafen and his colleagues from the University of Zürich used fruit flies to investigate the role of the insulin-signalling pathway and in particular a molecule called FOXO. If insulin signalling is reduced, for example by starving developing fly larvae, FOXO activity increases; this then reduces the number of cells in the developing flies, causing them to be smaller.

Mammals have similar a signalling pathway, and it has been suggested to have a role in tumour formation. Hafen's work gives us more insights into how disruption of FOXO function can lead to cancer.

The researchers used a combination of genetic techniques, over expressing FOXO in parts of the fly and analysing flies that contained no functional FOXO protein, to investigate what FOXO does. They found that flies with no functional FOXO looked normal but were more sensitive to oxidative stress, thought to be a cause of ageing. Increasing the amounts of highly active FOXO protein in the developing fly eye caused many of the eye cells to die. However, the real clue to FOXO's function came from studying the effect of removing functional FOXO protein from flies that have a reduced ability to signal downstream of insulin.

Normally, reducing insulin signalling in developing flies causes these flies to become smaller as they have fewer, smaller cells. Yet without FOXO, these flies do not suffer such a severe size reduction. This is because they have more cells than normal insulin signalling pathway mutants. These experiments suggest that FOXO plays a role in reducing the number of cells in the developing fly if insulin is not present, by inhibiting cell division.

Hafen and his co-authors write, "In this study we provide genetic evidence that the Drosophila FOXO homolog, dFOXO is an important downstream effector of Drosophila insulin signalling and regulator of stress resistance".

The insulin-signalling pathway may provide a crucial link between nutrient availability, stress and growth, thus allowing animals to respond appropriately to their environment.
-end-
This article is freely available online, according to BioMed Central's policy of open access to research articles:
http://jbiol.com/content/2/3/20

The Drosophila Forkhead transcription factor FOXO mediates reduction in cell number associated with reduced insulin signaling Martin A. Jünger, Felix Rintelen, Hugo Stocker, Jonathan D. Wasserman, Mátyás Végh, Thomas Radimerski, Michael E. Greenberg and Ernst Hafen.
Journal of Biology 2003, 2:20 (published 6th August 2003)

Please publish the URL in any news report so that your readers will be able to read the original paper.

Contact one of the authors Dr. Ernst Hafen for further information about this research, hafen@zool.unizh.ch

Alternatively contact Gemma Bradley by email at press@biomedcentral.com or by phone on 44-207-323-0323.

Journal of Biology (http://jbiol.com) is published by BioMed Central (http://www.biomedcentral.com), an independent online publishing house committed to providing immediate free access to peer-reviewed biological and medical research. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science. In addition to open-access original research, BioMed Central also publishes reviews and other subscription-based content.

BioMed Central

Related Stress Articles from Brightsurf:

Stress-free gel
Researchers at The University of Tokyo studied a new mechanism of gelation using colloidal particles.

Early life stress is associated with youth-onset depression for some types of stress but not others
Examining the association between eight different types of early life stress (ELS) and youth-onset depression, a study in JAACAP, published by Elsevier, reports that individuals exposed to ELS were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.

Red light for stress
Researchers from the Institute of Industrial Science at The University of Tokyo have created a biphasic luminescent material that changes color when exposed to mechanical stress.

How do our cells respond to stress?
Molecular biologists reverse-engineer a complex cellular structure that is associated with neurodegenerative diseases such as ALS

How stress remodels the brain
Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

How plants handle stress
Plants get stressed too. Drought or too much salt disrupt their physiology.

Stress in the powerhouse of the cell
University of Freiburg researchers discover a new principle -- how cells protect themselves from mitochondrial defects.

Measuring stress around cells
Tissues and organs in the human body are shaped through forces generated by cells, that push and pull, to ''sculpt'' biological structures.

Cellular stress at the movies
For the first time, biological imaging experts have used a custom fluorescence microscope and a novel antibody tagging tool to watch living cells undergoing stress.

Read More: Stress News and Stress Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.