Researchers from King's College London have provided the first experimental evidence confirming a great British mathematician's theory of how biological patterns such as tiger stripes or leopard spots are formed.
The study, funded by the Medical Research Council and to be published online in Nature Genetics, not only demonstrates a mechanism which is likely to be widely relevant in vertebrate development, but also provides confidence that chemicals called morphogens, which control these patterns, can be used in regenerative medicine to differentiate stem cells into tissue.
The findings provide evidence to support a theory first suggested in the 1950s by famous code-breaker and mathematician Alan Turing, whose centenary falls this year. He put forward the idea that regular repeating patterns in biological systems are generated by a pair of morphogens that work together as an 'activator' and 'inhibitor'.
To test the theory the researchers studied the development of the regularly spaced ridges found in the roof of the mouth in mice. Carrying out experiments in mouse embryos, the team identified the pair of morphogens working together to influence where each ridge will be formed. These chemicals controlled each other's expression, activating and inhibiting production and therefore controlling the generation of the ridge pattern.
The researchers were able to identify the specific morphogens involved in this process – FGF (Fibroblast Growth Factor) and Shh (Sonic Hedgehog – so-called because laboratory fruit flies lacking the fly version have extra bristles on their bodies). They showed that when these morphogens' activity is increased or decreased, the pattern of the ridges in the mouth palate are affected in ways predicted by Turing's equations. For the first time the actual morphogens involved in this process have been identified and the team were able to see exactly the effects predicted by Turing's 60-year-old speculative theory.
Dr Jeremy Green from the Department of Craniofacial Development at King's Dental Institute said: 'Regularly spaced structures, from vertebrae and hair follicles to the stripes on a tiger or zebrafish, are a fundamental motif in biology. There are several theories about how patterns in nature are formed, but until now there was only circumstantial evidence for Turing's mechanism. Our study provides the first experimental identification of an activator-inhibitor system at work in the generation of stripes – in this case, in the ridges of the mouth palate.
'Although important in feeling and tasting food, ridges in the mouth are not of great medical significance. However, they have proven extremely valuable here in validating an old theory of the activator-inhibitor model first put forward by Alan Turing in the 50s.
'Not only does this show us how patterns such as stripes are formed, but it provides confidence that these morphogens (chemicals) can be used in future regenerative medicine to regenerate structure and pattern when differentiating stem cells into other tissues.
'As this year marks Turing's centenary, it is a fitting tribute to this great mathematician and computer scientist that we should now be able to prove that his theory was right all along!'
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NOTES TO EDITORS
Copies of the paper available on request – please contact press@nature.com
About King's College London (www.kcl.ac.uk)
King's College London is one of the top 30 universities in the world (2011/12 QS World University Rankings), and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.
King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.
The College is in the midst of a five-year, £500 million fundraising campaign – World questions|King's answers – created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign's three priority areas are neuroscience and mental health, leadership and society, and cancer. More information about the campaign is available at http://www.kcl.ac.uk/kingsanswers.
About Medical Research Council (http://www.mrc.ac.uk)
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century.
Journal
Nature Genetics