Alfonso Martinez Arias

I am interested in the structure and function of Living Matter with a special focus in the processes that create tissues and organs from single cells through the interactions of intrinsic programmes of gene expression with chemical and mechanical signalling. In this context, the questions that interest me at the moment are:

  • Stochastic and deterministic processes in cell fate decisions;
  • The nature of genetic programs in animal development;
  • Cell and tissue dynamics during morphogenesis;
  • Mechanochemical signalling in cell ensembles;
  • The relationship between Gene and Cell Regulatory Networks (GRNs and CRNs);
  • The evolution of body plans.

Over the last few years my group has developed a new model system for the study of early mammalian development that we call ‘gastruloids’ and I like to use it to think about the issues posed above.

Gastruloids emerge when small, specified numbers of mouse Pluripotent Stem cells (PSCs) are placed in defined culture conditions. Under these conditions they aggregate and initiate a sequence of pattern forming events mirroring the events that take place in the embryo: symmetry breaking, gastrulation-like movements, axial specification and germ layer organization. Gastruloids can be cultured for up to seven days to reach a stage comparable to E9.0 in the mouse embryo and exhibit a similar organization of organ primordia including two orthogonal axes and bilateral asymmetries. They represent a new model system for mammalian development that can be used to gain insights into the process of gastrulation and the emergence of the body plan.

Much of our work takes place at the interface of developmental biology and engineering as I believe that it is here that we shall uncover processes that will improve our ability to control  the differentiation of stem cell into specific cell types.

References

1. 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.

2. Turner DA, Girgin M, Alonso-Crisostomo L, Trivedi V, Baillie-Johnson P3, Glodowski CR,  Hayward PC, Collignon J, Gustavsen C, Serup P, Steventon B, P Lutolf M, Martinez Arias A. (2017) Anteroposterior polarity and elongation in the absence of extraembryonic tissues and spatialy organized signaling in Gastruloids, mammalian embryonic organoids. Development 144, 3894-3906.

3. Beccari, L., Moris, N., Girgin, M., Turner, D., Baillie-Johnson, P., Cossy, A.C., Lutolf, M., Duboule, D. and Martinez Arias, A. (2018) Multi-axial self organization properties of mouse embryonic stem cells gastruloids. Nature 562, 272-276.

4. van den Brink,S., Alemany,A., van Batenburg,V. Moris, N., Anlas, K., Blotenburg, M., Turner, D., Vivié, J., Martinez Arias, A. and Oudenaarden, A. (2020) Single cell and spatial transcriptomics reveals somitogenesis in gastruloids. Nature doi: 10.1038/s41586-020-2024-3.