The work of our colleagues Christian SchrÃ¶eter and Pau RuÃ© on the integration of FGF signalling and GATA4,6 activity in a mouse ES cell model of Primitive Endoderm specification has just been published in Development (http://dev.biologists.org/content/142/24/4205) The specification of Primitive Endoderm requires an integration of a transcriptional input provided by a transcription factor of the GATA family and FGF signalling. In this work, a combination of live imaging, quantitative analysis and modelling reveals that FGF signalling sets up a threshold for the activity of GATA. The work also uncovers a simple bistable system which can account for the experimental observations and also provides a framework to think about events in the embryo.
The lab also published a video account of how to make gastruloids (http://www.jove.com/video/53252/generation-aggregates-mouse-embryonic-stem-cells-that-show-symmetry ). In the organoid world reproducibility is all and, for this reason, following the publication of our finding about symmetry breaking and axial elongation from ES cells (http://dev.biologists.org/content/141/22/4231.full ), we have now made a detailed account of the protocol. You might also want to have a look at our perspective on the organoid field from the point of view of developmental biology (http://onlinelibrary.wiley.com/doi/10.1002/bies.201500111/abstract ) -maybe not that much self organization. And while on this topic, watch this space; coming soon is a study of the early events in the patterning of the gastruloids.
Turner DA, Baillie-Johnson P, Martinez Arias A. Organoids and the genetically encoded self-assembly of embryonic stem cells. BioEssays. 2015. doi:Â 10.1002/bies.201500111
Baillie-Johnson P, van den Brink SC, Balayo T, Turner D A, Martinez Arias A. Generation of Aggregates of Mouse Embryonic Stem Cells that Show Symmetry Breaking, Polarization and Emergent Collective Behaviour In Vitro. J. Vis. Exp. 2015 (105), e53252, doi:10.3791/53252
Freyer L, SchrÃ¶ter C, Saiz N, Schrode N, Nowotschin S, Martinez-Arias A, Hadjantonakis A-K. A loss-of-function and H2B-Venus transcriptional reporter allele for Gata6 in mice. BMC Developmental Biology 2015, 15:38Â doi:10.1186/s12861-015-0086-5
Turner DA, Hayward PC, Baillie-Johnson P, RuWnt/Î²-catenin and FGF signalling direct the specification and maintenance of a neuromesodermal axial progenitor in ensembles of mouse embryonic stem cells.
van den Brink SC, Baillie-Johnson P, Balayo T, Hadjantonakis A-K, Nowotschin S, Turner DA, Martinez Arias A. Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells.
Christoforou A1, Martinez Arias A, Lilley KS. Determining Protein Subcellular Localization in Mammali an Cell Culture with Biochemical Fractionation and iTRAQ 8-Plex Quantification. Methods Mol Biol. 2014;1156:157-74.
Fischer SC, Blanchard GB, Duque J, Adams RJ, Arias AM, Guest SD, Gorfinkiel N. (2014) Contractile and mechanical properties of epithelia with perturbed actomyosin dynamics. PLoS One. 2014 Apr 23;9(4):e95695. doi: 10.1371/journal.pone.0095695.Â
Turner, DT., Trott, J., Hayward, P. Rue, P and Martinez Arias, A. (2014) An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells.iBiology Open I (2014) 000, 1â€“13 doi:10.1242/bio.20148409
Turner, DT., Mackenzie, J., Davies, E. and Martinez Arias, A. (2013) Brachyury cooperates with Wnt/ÃŸ-Catenin signalling to specify individual cell velocities during Primitive Streak differentiation of mouse ES cells. bioRxivdoi: 10.1101/003871
Trott, J. and Martinez Arias, A. (2013) Single cell lineage analysis of the exit of pluripotency in mouse Embryonic Stem cells. Biology Open 2:1049-56. doi: 10.1242/bio.20135934.
MuÃ±oz-Descalzo, S., Rue, P., Faunes, F., Hayward, P., Jakt, L.M., Balayo, C., Garcia Ojalvo, J. and Martinez Arias, A. (2013) A competitive protein interaction network buffers Oct4-mediated differentiation to promote pluripotency in embryonic stem cells. Mol. Sys. Biol. 9:694. doi: 10.1038/msb.2013.49.
Martinez Arias, A., Nichols, J. and Schroeter, C. (2013) A molecular basis for developmental plasticity of early mammalian embryos. Development 140, 3499-3510.
Faunes, F., Hayward, P., MuÃ±oz Descalzo, S., Chaterjee, S., Balayo, T., Trott, J., Ferrer-Vaquer, A., Hadjantonakis, AK., Dasgupta, R. and Martinez Arias, A. (2013) A membrane associated ÃŸ-catenin/Oct4 complex is associated with ground state pluripotency in mouse Embryonic Stem Cells. Development 140, 1171-1183.
Klein, T., Schneider, M., Troost, T., Grawe, F. andÂ Martinez-Arias, A. (2012) Activation of Notch in lgd mutant cells requires the fusion of late endosomes with the lysosome. J Cell Science. 126, 645-656.
Chalut KJ, HÃ¶pfler M, LautenschlÃ¤ger F, Boyde L, Chan CJ, Ekpenyong A, Martinez-Arias A, Guck J (2012) Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells. Biophysical J. 103, 2060-2070.
Garcia Ojalvo, J. and Martinez Arias, A. (2012) Towards a statistical mechanics of cell fate decisions. Curr Op. in Genet. and Dev. 22, 1-8.
Luo, Y.Â Lim, C., Nichols, J., Martinez Arias, A., and Wernisch, L. (2012) Cell signalling regulates potential landscapes in ES cell populations. Roy. Soc Interface. vol. 10 no. 78 20120525
MuÃ±oz Descalzo, S., Rue, P., Garcia Ojalvo, J. and Martinez Arias, A. (2012) Correlations between the levels of Oct4 and Nanog as a signature for naÃ¯ve pluripotency in mouse ES cells. Stem Cells 30, 2683-2691.
Chalancon G, Ravarani CN, Balaji S, Martinez-Arias A, Aravind L, Jothi R, Babu MM. (2012) Interplay between gene expression noise and regulatory network architecture. Trends in Genet. 28, 221-232.
de Navascues, J., Perdigoto, C., Bardin, A., Martinez Arias, A. and Simons, B. (2012) Drosophila midgut homeostasis results from neutral competition between symmetrically dividing intestinal stem cells. EMBO J. 31:2473-2485.
Lada, K. Gorfinkiel, N. and Martinez Arias, A. (2012) Interactions between the amnioserosa and the epidermis revealed by the function of the ushaped gene. Biology Open. 1, 353-361.
MuÃ±oz Descalzo, S. and Martinez Arias, A. (2012). The structure of Wntch signalling and the resolution of transition states in development. Seminars in Cell and Dev Biol.Â 23, 443-449.
MuÃ±oz 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.
Trott, J., Hayashi, K., Surani, A., Babu, M. and Martinez Arias, A. (2012) Dissecting ensemble networks in ES cell populations reveals micro-heterogeneity underlying pluripotency. Molecular Biosystems 8, 744-752.