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The self engineering of the mammalian embryo: a synthetic approach
Alfonso Martinez-Arias, Professor
Department of Genetics, University of Cambridge
IBBME Research Theme
The recurrent emergence of tissues and organs during development suggest the existence of programs that are triggered at fertilization and unfold in space and time during embryogenesis.
The genetic analysis of this process has provided support for this notion and led to the identification of the pieces that run the program: genes and proteins.
However, the building of tissues and organs is more a matter of cells than of genes (1) and one can construe this as an engineering process in which the genes are instructions to build cells which are the actual decoders and, at the same time, builders of the system. The mammalian embryo is a particular extreme example of this, as it starts with a small number of cells, about 400, and develops shape and pattern as it increases its cellular mass.
Over the last few years we have been using embryonic stem (ES) cells to address these questions.
ES cells are are clonal derivatives from the epiblast of preimplantation mammalian embryos which, after prolonged culture, can be differentiated into all cell types of an organism.
We have found that, under defined culture conditions, small and precise numbers of ES cells will form aggregates that develop by mirroring events in the embryo (2-4). These aggregates, that we call ‘gastruloids’ undergo symmetry breaking, gastrulation like processes and germ layer organization and differentiation followed by axial organization and elongation.
Analysis of these process suggest that gastruloids are following a program that encodes time and space autonomously.
We are using gastruloids to explore how a mammalian embryo engineers itself from the cellular perspective and I shall be discussing our findings and how can we harness them to understand and engineer the emergence of tissues and organs in the embryo.
1. Martinez Arias, A. (2016) Of codes and machines in Biology. Blog post https://amapress.gen.cam.ac.uk/?p=1800
2. van den Brink, S., Baillie-Johnson, P., Balayo, T., Hadjantonakis, AK., Nowotschin, S., Turner, DA. And & Martinez Arias, A. (2014) Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse ES cells. Development 141, 4231-4242.
3. Turner, DT., Hayward, P., Baillie Johnson, P., Broome, R., Rue, P., Faunes, F. and Martinez Arias, A. (2014) Wnt/ß-catenin and FGF signalling direct the specification and maintenance of a neuromesodermal axial progenitor in ensembles of mouse ES cells. Development 141, 4242-4253.
4. Turner, D., Girgin, M., Alonso-Crisostomo, L., Baillie-Johnson, P., Glodowski, C. R., Hayward, P., Collignon, J., Gustavsen, C., Serup, P., Steventon, B., et al. (2017). Anteroposterior polarity and elongation in the absence of extraembryonic tissues and spatially localised signalling in Gastruloids, mammalian embryonic organoids. Development In press.
Dr. Alfonso Martinez-Arias obtained his PhD from the University of Chicago, and was a postdoc with Peter Lawrence at the Laboratory of Molecular Biology in Cambridge University.
In 1983 Dr. Martinez-Arias obtained his PhD from the University of Chicago and then moved to the UK where in 1987 was awarded a Wellcome Trust Senior Fellowship at Cambridge, where he became a Professor of Developmental Mechanics in 2002. He is an elected member of EMBO and in 2012 was awarded the Waddington medal for his contributions to British developmental biology.
His laboratory uses methods at the interface of physics and biology to understand the principles that govern embryonic development.
Dr. Martinez-Arias’ has over 140 publications which have been cited over 14,000 times. He is also a co-author of the influential textbook Principles of Development.