Prioritising brain over body

05 August 2011

Louise Cheng (first author) and Alex Gould (corresponding author) of a paper in the journal Cell, 5 August 2011

Image: Louise Cheng and Alex Gould from the National Institute for Medical Research ©  NIMR

New research has shed light on how the growth of the brain is protected over other organs during periods of starvation. The work, published in the journal Cell, also has promising implications for understanding the growth of cancerous tumours. 

A team of scientists from the Medical Research Council National Institute for Medical Research (NIMR) and Cancer Research UK London Research Institute (both now part of the Francis Crick Institute), has found that a specific gene protects the growth of the central nervous systems of developing fruit flies when food is scarce.

The growth of most tissues in developing animals is matched to the availability of nutrients in the diet.  Some tissues, however, are less sensitive to the withdrawal of nutrients than others. One illustration of this is intra-uterine growth restriction (IUGR) in humans, when lack of food or a faulty placenta restricts the growth of the foetus, the undersized child is sometimes born with a relatively large head. This is because the growth of the brain has been protected or spared at the expense of other organs.

The team found that the effect holds true in fruit flies where the brain is also the most highly protected organ when nutrients are in short supply. As more than two thirds of human disease genes are shared with fruit flies, their work has shed light on how the brains and nervous systems of human foetuses could be protected.

The scientists withdrew dietary nutrients from the flies at 'the late-larval stage' when much of the growth during the insect life cycle takes place.  They noticed that this shut down growth of most of the body, apart from the stem cells that build the fly's brain. Remarkably, these neural stem cells were able to continue to grow normally in the absence of dietary nutrients.  The team then found that a specific gene, known as Anaplastic Lymphoma Kinase or ALK, protects brain growth by forcing two key chemical processes to work even when nutrients are scarce.

An identity parade of Drosophila organs ("the usual suspects") with their heights representing the percentages of growth spared during nutrient restriction.

The usual suspects: an identity parade of Drosophila fruit fly organs with their heights representing the percentages of growth spared during nutrient restriction. (Click to view larger image)
© Alex Gould and Andrew Bailey

Alex Gould from the MRC National Institute for Medical Research, who led the study, explained why other tissues were not also protected when nutrients were in short supply: "Other tissues don't appear to have this type of ALK-pathway - or at least it doesn't function in the same way as it does in neural stem cells. One way we were able to show this was by doing an experiment involving a growing tissue that's not normally spared from the effects of withdrawing nutrients - the salivary gland. When we activated ALK in the salivary gland, it was converted into a tissue that, like the brain, is able to grow a substantial amount without dietary nutrients."

Image shows how central nervous system stem cells can grow during nutrient restriction while many other tissues cannot

Central Nervous System stem cells can grow during nutrient restriction while many other tissues cannot (Click to view larger image)
© Alex Gould

 

 

 

 

 

 

 

 

 

Alex Gould also explained that they found similarities between the continuing growth of the fly brain during starvation and the expansion of tumours in mammals: "There is clearly a connection between the processes that give neural stem cells a growth advantage during fly development and those processes that give human cancer cells a growth advantage over healthy cells.

"Anaplastic Lymphoma Kinase was first identified in human lymphomas, and has subsequently been found in many other types of cancer. So the involvement of ALK both in organ sparing and in cancer is intriguing. It suggests that, at least in some cases, we might view cancer as the dark side of organ sparing." 

 

Original article: Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila. Louise Y. Cheng, Andrew P. Bailey, Sally J. Leevers, Alex P. Gould.

  • Cheng et al., Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila,Cell (2011)-146 (3):435-447
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