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Embryos, stem cells, and gastruloids: a spatialist interpretation of developmental biology an animation by Stefano Vianello

The challenge faced by developmental biologists is not an easy one: the embryo is a system under continuous change, where single cells navigate space, time, states and fates accordingly to mechanisms that are still poorly understood. Yet, these mechanisms must clearly work in that they consistently allow for the robust and reliable generation of functional adult living systems. How do we reconcile the quickly-changing reality of the developing embryo with the requirements of precise in vitro experimentation?

The short animation above introduces this topic and highlights the mutual relationship between in vivo and in vitro developmental models. By reinterpreting Italian photographer Ugo Mulas’ famous picture series, we here transpose Lucio Fontana’s spatialist interpretation of art to the developing embryo. Just as Fontana warped the dimensionality of the canvas by slashing it with a razor, developmental biologists interrupt the inexorable progression of developmental time by extracting cells from the inner cell mass. This population we call “embryonic stem cells”. From these the AMA lab has developed protocols that allow the generation of self-organising aggregatess: the gastruloids. Developed by learning from the embryo, gastruloids in turn allow to learn about the embryo, and represent in vitro systems where one can investigate in a controllable way the logic whereby cells interpret space and time.

This video has been featured at http://www.embryoengineering2016.org, Paris, France.

 Credits:

  • Music: “Soft mischief” by Jay Man, ourmusicbox.com
  • Mouse early development: Sylvain Bessonard, Institut Pasteur, Paris, France
  • Picture series: Ugo Mulas “Lucio Fontana” (1964)

 

Reconstructing early stages of embryo development
Reconstructing the early stage of mammalian development using embryonic stem cells, showing that a critical mass of cells – not too few, but not too many – is needed for the cells to being self-organising into the correct structure for an embryo to form.

 

Landscapes and Embryos
A film from A. Martinez Arias

A trip through some landmarks of Developmental Biology against the background of the Goldberg variations played by Glenn Gould, which evoke the order and harmony of the events that build embryos. The film takes the notion that developmental biologists see the making of the organisms unfolding in the vision of the genes or the cells and grows it through images of the various systems that have been used to understand cell fate specification and morphogenesis. The film introduces you to the world of how cells make embryos starting with the chick embryo, the grand classic of developmental biology. Then it introduces you to the fruit fly Drosophila melanogaster whose genetics has revealed to us the molecular make up of developmental systems and their cellular basis as well as the homeotic genes, which uncovered one of the most intriguing aspect of conservation in nature, the structure and deployment of the Hox genes. The organization, expression and conservation of these genes across all organisms confirms suspicions from comparative embryology that embryos are intimately related, particularly at their early stages, and that they converge in a stage with an anteroposterior segmentation pattern, a landmark of all organisms from insects to mammals. The film ends up by exploring issues of mammalian development and embryonic stem cells which take us back to the abstractions in the mind of the developmental biologists.

 

A Waddington landscape I
A film by A. Martinez Arias and S. Muñoz Descalzo

In this short animation we take the original idea of the ‘epigenetic landscape’ by CH Waddington and put it into motion, as he probably conceived it in his mind. Waddington saw cells as pebbles rolling down a mountain with hills and valleys. The bottom of the valleys represents cell or differentiation states. Our rendition keeps close to the notions of Waddington except that it looks at the starting point not as a summit but rather as the crater of a volcano (for some details of the summit see Martinez Arias, A. and Brickman, J. (2011) Gene expression heterogeneities in embryonic stem cell populations: origin and function. Curr.Op. in Cell Biology 23, 650-656)

 

A Waddington landscape II
A film by A. Martinez Arias and S. Muñoz Descalzo

In this second rendition of Wadington’s ‘epigenetic landscape’, we introduce two variations which we believe reflect some important developmental processes. The first one is that the valleys and the hills, the actual landscape that cells will traverse, are not predermined, that the cells make them as they move along the developmental landscape. The second notion is that at every bifurcation of the landscape there is a binary decision (green or red), that this decisions are helped by an iterative process which is likely to involve Notch and Wnt signalling (see Muñoz Descalzo, S., de Navascues, J and Martinez Arias, A. (2012) Wnt/Noch signaling: an integrated mechanism regulating transitions between cell states. Bioessays 34, 110-118.)

 

Fluctuations in Nanog Expression

This is a movie from our paper on the dynamics of ES cells (Kalmar T., Lim, C., Hayward, P., Muñoz Descalzo, S., Garcia Ojalvo, J. and Martinez Arias, A. (2009) Regulated fluctuations in Nanog expression mediate cell fate decisions in embryonic stem cells. PLoS Biol 7(7): e1000149. doi:10.1371/journal.pbio.1000149). It does show fluctuations in Nanog expression and does represent much of the spirit of the research in our laboratory.

 

Mouse Embryonic Stem Cells

Transient expression of a fluorescently labelled differentiation protein under Doxycyline control in mouse Embryonic Stem Cells. Courtesy of Christian Schröter

 

Epithelial to Mesenchymal Transition

These are mouse embryonic stem cells expressing a fluorescent reporter of Wnt/Beta-Catenin activity. As they are differentiated towards mesoderm, there is a huge increase in reporter activity and cells begin the process of an epithelial to mesenchymal transition (EMT). Courtesy of David Turner.

β-catenin mutant videos

  These are three videos from our recent publication in Development (“A membrane-associated β-catenin/Oct4 complex correlates with ground-state pluripotency in mouse embryonic stem cells.” Development. 2013 Mar;140(6):1171-83. doi: 10.1242/dev.085654) which highlight the behaviour of wildtype and ß-catenin mutant cells in … Continue reading

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