Timer genes control brain size

May 29 2008

Experiments using fruit flies have helped a team at the MRC National Institute for Medical Research to identify genes that control how large the developing brain becomes.

Within the growing brain, stem cells divide to produce more and more neurons until an upper limit is reached. Dr Cédric Maurange, Dr Louise Cheng and Dr Alex Gould have found that 'timer' genes tell stem cells when and how to stop dividing, thus preventing the brain from growing too large. This is important for building a fully functioning brain. The research is published in Cell.

Dr Alex Gould who led the research explained:

''The gene timer system of the fruit fly appears to control how many neurons the brain contains and therefore how big it becomes. If there is a mutation in one of the 'timer' genes the brain grows extra clumps of cells that somewhat resemble brain tumours. ''

The study found that two timer genes, named Castor and Seven-up, together with a larger network of interacting genes, regulate the time at which neural stem cells either stop dividing or are destroyed during brain development.

Dr Gould said:

''This discovery has relevance for future stem-cell based therapies in two ways. Firstly, while we know how to grow massive quantities of neurons from neural stem cells in a petri-dish, it's also important to understand how to stop them growing if they are to be transplanted safely into a human brain.''

''Secondly, we know that the human brain retains a few neural stem cells into adulthood. If we could learn how to influence the internal clock of these cells it might be possible to rejuvenate them so they can make replacement neurons. These could then be used to help repair damage caused by neurodegenerative conditions like Alzheimer's or Parkinson's disease.''

{IMAGE}

The fruit fly, Drosophila, shares many genes linked to growth and development with mammals, making it an ideal organism to study how genes work in humans. Genes equivalent to Castor and Seven-up are known to be present in the human genome. Dr Gould said the next step for this research would be to find out whether these genes have the same role in brain growth control in mammals as they do in the fruit fly.

Original research paper: Temporal Transcription Factors and Their Targets Schedule the End of Neural Proliferation in Drosophila by C. Maurange, L. Cheng and A. P. Gould is published in Cell.