MRC National Institute for Medical Research, London
Science for Health
Gene network that builds tissues revealed
20 January 2012
A network of interacting genes that control how cells are organised into tissues has been revealed by scientists at NIMR and UCL. The research is published in Cell.
How the diversity and pattern of different types of cells are generated in embryos is a long-standing question for medical researchers. In many tissues, signals called ‘morphogens’ organize cell pattern. The new research explains how morphogens accomplish this task.
James Briscoe (pictured), from NIMR's Division of Developmental Biology, teamed up with mathematicians from UCL led by Karen Page, in a collaboration funded by the Wellcome Trust, to look at the way in which the spinal cord develops in embryos. They found that a morphogen signal, known as 'Shh', governs the specific pattern of nerve cells in the tissue by triggering a complex network of genes called transcription factors. Shh activated some of the 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, the team at UCL created a mathematical model that reconstructed the complex network of interactions between the transcription factors. This allowed the two groups 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.
Understanding how patterns of cells are produced in embryonic tissues is one of the central questions of developmental 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.
Karen Page
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 sheds new light on the formation of nervous system and also opens the door to tissue engineering in the future. 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 it.
James Briscoe
Ventral neural tube patterning by graded Shh signalling
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Original article
Nikolaos Balaskas, Ana Ribeiro, Jasmina Panovska, Eric Dessaud, Noriaki Sasai, Karen M. Page, James Briscoe, and Vanessa Ribes (2012)
Gene regulatory logic for reading in the vertebrate neural tube the Sonic Hedgehog signaling gradient
Cell, 148:273-284. Publisher abstract.
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