The way in which a network of interacting genes control how cells are organised into tissues has been revealed for the first time by a collaboration between biomedical scientists working at MRC's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) and mathematicians from UCL, London.
The researchers, led by Dr James Briscoe of NIMR, looked at the way in which the spinal cord develops in embryos, asking what controls the arrangement of the different types of nerve cells that make up the cord. They found that an external signal, called 'Shh', governs the specific pattern of cells in the tissue by triggering a complex network of genes called transcription factors. Shh activated some of transcription factors and these then deactivated others. As a result only a subset of transcription factors were active in any one cell, creating specific types of cells depending on how much Shh they were exposed to.
Using this knowledge, Dr Karen Page's team at UCL created a mathematical model that reconstructed the complex network of interactions between the transcription factors. This allowed the team to investigate the network in isolation from other parts of the cell and confirmed that the network is responsible for the pattern of cells in the spinal cord. It also revealed that the structure of the network makes cells less susceptible to fluctuations in Shh, locking-in the identity of cells so that they don't change if Shh is decreased. This helps explain the embryonic development of the spinal cord and suggests why it is so precise and reliable.
Dr Page said: "Understanding how patterns of cells are produced in embryonic tissues is one of the long standing questions in development biology. But it's difficult to answer this question with biology alone, as cells and tissues are very complex. Bringing mathematical modelling to the problem gives us a chance to focus on specific parts and systems within cells - really sharpening our understanding of what is happening."
Dr Briscoe suggested that similar mechanisms are also likely to be at work during the development of other tissues in the body: "External signals and networks of transcription factors have been found in many embryonic tissues. Although the identities of the factors and the details of the networks differ, our work showing that a network of interacting transcription factors can transform an external signal into a complex pattern of different cell types in the spinal cord, raises the possibility that similar strategies are used in other tissues".
The study also opens the door to tissue engineering in the future. Dr Briscoe said: "By learning how the nervous system is built in embryos, we hope to be able to mimic these processes using stem cells in the laboratory. This might allow us to produce nerve tissue in a dish in order to study diseased and damaged nervous systems and perhaps, one day, to repair them".
Original article: Nikolaos Balaskas, Ana Ribeiro, Jasmina Panovska, Eric Dessaud, Noriaki Sasai, Karen M. Page, James Briscoe, and Vanessa Ribes (2012)