Parameterisation of developmental networks to understand periodic patterning

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Periodic patterns are a fundamental feature of vertebrate anatomical organisation. Such patterns, arising rapidly in the embryo, have long been suspected to involve the action of a system involving coupled short range activatory and long range inhibitory processes. Five decades of theory have clearly shown that a system of such interactions can yield self-organisation and the production of organic-looking patterns, at least on a computer screen. While developmental biology, genetics and molecular biology have begun to explore what the components of such systems might be, this has not yet advanced to the stage at which we can properly test or understand its operation. To move forward a quantitative molecular approach is needed to provide the hard data to test the theory and illuminate its operation in a defined system.

We will build on our recent work in avian genetics and developmental biology to establish a structural network of signalling interactions that patterns the developing chicken skin. We will produce a mathematical model that describes these interactions and which takes into account realities in biological processees, such as defining the production of proteins in terms of transcription and translation. We will then measure the relevant molecular parameters, such as diffusion and decay rates of proteins in the system, to input into the model. The output of this simulation will inform us as to how well it can explain the size and spacing of pattern elements in the skin, as well as the timescale of pattern emergence. The simulations will be used to predict the effects of alterations to molecular parameters and signal intensities, and these predictions will then be tested experimentally to refine and evaluate the model's predictive power. This iterative experimental/modelling approach will then be expanded to incorporate more entities into the network, if necessary, and to explore the malleability and robustness of the system.

This is primarily a fundamental science project that aims to produce insights into the mechanisms of embryonic development and pattern formation. The immediate impact will chiefly be upon the academic beneficiaries and the general public, with industrial benefits arising from our work on the genetics of feather control, which is clearly documented as a very beneficial trait for egg and meat production, and animal welfare, in hot conditions (either chronic or acute). Our explorations of the recessive scaleless mutant have resulted in a genetic test for the mutation which will be reported along with our findings in development, signalling and pattern formation. This test can be used for rapid introgression of this trait into any desired line, particularly anticipated to be useful for the broiler chicken industry.

The public impact of this project upon the public will be enhanced by the 'real-world' nature of the model system studied; the distribution of hair of different types across the body. This model is easily appreciated by a lay audience and, combined with the striking images produced in studies of spatial patterning, this area is ideal for public engagement activities. In this regard the use of cultured skin and computer simulation where appropriate in the project, rather than Protected Animals, will aid public engagement and acceptance.

Academic beneficiaries will gain new insights into the basis of vertebrate development and the way in which computational tools can be used in conjunction with wet experiments to attain a deeper understanding of biological phenomena. In addition, the specific signalling pathways under study are relevant to the development of many vertebrate organs and will stimulate studies regarding the integration of these signals in a range of tissues.