The model is aesthetically beautiful, because the rules are so simple and yet they are able to predict the complex branching patterns of these structures.
- Ben Simons
Branching patterns occur throughout nature – in trees, ferns and coral, for example – but also at a much finer scale, where they are essential to ensuring that organisms can exchange gases and fluids with the environment efficiently by the maximising the surface area available.
For example, in the small intestine, epithelial tissue is arranged in an array of finger-like protrusions. In other organs, such as kidney, lung, mammary glands, pancreas and prostate, exchange surfaces are packed efficiently around intricate branched epithelial structures.
“On the surface, the question of how these structures grow – structures that may contain as many as 30 or 40 generations of branching – seems incredibly complex,” says Professor Ben Simons, who led the study, published today in the journal Cell. Professor Simons holds positions in the University of Cambridge’s Cavendish Laboratory and Wellcome Trust/Cancer Research UK Gurdon Institute.
This classic problem of ‘branching morphogenesis’ has attracted the attention of scientists and mathematicians for centuries. Indeed, the mathematical underpinnings of morphogenesis – the biological process that causes organisms to develop their shape – was the subject of D’Arcy Wentworth Thompson's classic text, published in 1917 by Cambridge University Press. Thompson had been a student at Cambridge, studying zoology at Trinity College, and briefly worked as a Junior Demonstrator in Physiology.
During development, branching structures are orchestrated by stem-like cells that drive a process of ductal growth and division (or ‘bifurcation’). Each subsequent branch will then either stop growing, or continue to branch again. In a study published in Nature earlier this year, Professor Simons working in collaboration with Dr Jacco van Rheenen at the Hubrecht Institute in Utrecht showed that, in the mammary gland, these processes of division and termination occur randomly, but with almost equal probability.
“While there’s a collective decision-making process going on involving multiple different stem cell types, our discovery that growth occurs almost at the flip of a coin suggested that there may be a very simple rule underpinning it,” says Professor Simons.
Image: Mammary gland, 4 day-old mouse
Reproduced courtesy of the University of Cambridge