Title Abstract

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Title

: Symmetry breaking and pattern formation in aggregates of mouse ES cells

Abstract

Embryonic Stem (ES) cells are clonal derivatives from the epiblast of preimplantation mammalian embryos which, after prolonged culture, they can be differentiated into all cell types of an organism.

Over the last few years, culture conditions have been found that can be used to steer these cells into defined ectodermal, mesodermal or endodermal derivatives. However, the resulting cells do not organize in space. Aggregates of ES cells in the form of Embryoid Bodies have been used to obtain particular cells types e,g blood and, under specific conditions have been shown to give rise to eye cups and forebrain like structrures. We have found that if the aggregates are of a certain size (which mimics that of a postimplantation epiblast), the aggregates undergo a spontaneous symmetry breaking event and initiate morphogenetic movements that resemble the early embryo including germ layer specification, gastrulation like movements and axial elongation. These observation will be the foundation of the seminar.

References 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.

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, 4242-425

Biography

As an undergraduate I studied Biology at the Universidad Complutense, Madrid (Spain). After graduating in 1977, I obtained a Fullbright scholarship to study in the US. Having developed an interest in Developmental Biology, though at the time I am not sure that this is what my interest was called, and the possibility that biological processes could be explained in terms of the physical

Sciences, in 1978 I went to the Department of Biophysics of the University of Chicago, Chicago (USA).

There I realized quickly that at the time, there was not enough Biology known to deal with at the interface with the physical Sciences; particularly in the realm of Developmental Biology. I also realized then the importance of genetic analysis as a first approximation to the solution of biological problems. My PhD, with Malcolm Casadaban, was an exercise learning Molecular Biology (Beta galactosidase fusions for the analysis of gene expression in yeast) and, in my spare time, learning as much classical Developmental Biology as possible. In 1983 I moved on to do a postdoc with Peter

Lawrence at the MRC Lab of Molecular Biology in Cambridge, UK. These were interesting days for developmental Biology and the LMB an excellent environment to develop my curiosity in these fields. In Cambridge, Peter Lawrence, Michael Akam and Michael Bate helped me develop a

framework to think about developmental problems that complemented the questions I had taken from Madrid to Chicago and which have stayed with me all along.

In 1987 I was awarded a Wellcome Senior Fellowship which I held until 2002 when I became a member of the University and since 2003 I am Professor of Developmental Mechanics. During this time, first in the department of Zoology and since 2000 in the Department of Genetics I have pursued my interests in the logic of animal development. I believe that Biology is about Living Matter and that organisms are not the result of cocktails of genes and proteins whimsically shuffled by

Evolution. Instead I believe that there are constraints and principles which determine the reproducible behaviours that we observe. One question that has become important to me is derived from the realization that at the molecular (and probably at the multicellular) level, there is a lot of stochasticity in the workings of the cell and yet the macroscopic level (tissues, organs, organisms) is very deterministic. How this transformation occurs is something that intrigues me very much.

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