#BSDBGenSoc2020 These days we all have other things in our minds, it is difficult to concentrate and many of my thoughts R w/ family anf friends in #Spain) but discussing our work, is an important part of our being and it is going to be important in the weeks and months to come.

While many, all, of us rather do al this in person, we are going to have to adjust in the weeks to come. #BSDBGenSoc2020 is a good way to explore how we are going to do it so, THANKS @_BSDB_ and @the_Node for organizing and running this.

My Tweetorial follows the phenomenal one from @TimFulton_1 @SteventonLab (with whom @AMA_Lab work closely) this morning and is very related.

And now onto the tweetorial in the form of a loooong thread.

#BSDBGenSoc2020 Modern developmental biology is more than describing the generation of and fate choices within germ layers. It is about understanding axial organization, scaling and coordination of those decisions.

We might think these days that #DevBio is @ mapping genes into cells when actually it is (and really has always been) @ mapping cells into space and time. Genes are a vehicle but cells are agents.

A clearest example of this is the all important process of #gastrulation, beautifully represented in this movie from Ray Keller about the process in Xenopus

Gastrulation is a process driven by cells where genes play a secondary role. The choreography/origami that you observe has been laid out by a partitioning of space before hand, through a combination of signals, but the process is driven by cells.

You may have noticed that in Xenopus, #gastrulation is, basically, a reorganization of thousands of cells and this is the same in most vertebrates with one exception: mammals.

Take the mouse. As the embryo is @ to undergo gastrulation, it only has about 400 cells (compared to >10000 in a frog) and then, it goes. About 36 hours later, a structure reflecting the body plan of the mouse emerges. Where does this organization come from?

What this observation tells us is that in mammals the process of gastrulation requires the coordination of an explosion of cell division with fate assignments and population scaling, all within a defined amount of time.

The traditional way to address these issues has been Genetics

…but if cells rather than genes are the masters, we need new approaches #NotAboutGenes.

Over the last few years, an approach has emerged that makes use of #Engineering principles. The elements for this are cells with genes used as perturbation tools.

In terms of mammalian developmental biology, the tools for this new approach are #StemCells and, from the point of view of early developmental events, Embryonic (ESCs), Trophectoderm (TS) and Extraembryonic endoderm (XEN) stem cells.

In my group, we've been interested in asking @ the potential of Embryonic Stem Cells (ESCs) to recapitulate developmental events. On their own, these cells generate EBs: disorganized multicellular structures with a random representation of derivatives of multiple germ layers

In contrast we have developed the #Gastruloid system where, starting from defined populations of ESCs, under precise culture conditions, structures emerged exhibiting features of early embryos dev.biologists.org/content/141/22…

In a collaboration with @Duboule and @TheLutolfLab groups, we further showed that #Gastruloids recapitulate the emergence of axially organized germ layers and temporal pattern of gene expression that mimic the embryo…..

….but these are not embryos, rather #Models of embryos nature.com/articles/s4158… The distinction is important

We also have shown that #Gastruloids can recapitulate the early symmetry breaking events of the embryo w/o extraembryonic tissues which are central for this during in utero development dev.biologists.org/content/144/21…

One speculation from these & unpublished experiments is that symmetry breaking is triggered by a mechanical input that is amplified chemically. See bit.ly/38R2Y1j bit.ly/38R2Y1j …neither conclusive IMO BUT clearly hinting at the role of mechanics

I suspect that we need to start tackling this mechanochemical events, for which there are frameworks at the level of single cells, but not yet at the level of cell populations

One observation from these studies is the absence of #morphogenesis in Gastruloids. Although we can see an (imperfect) genetic blueprint, there's a lack of multicellular organization i.e. morphogenesis can be decoupled from what we could call Genetic programs.

This decoupling means that we cannot know how much complexity, in terms of cell types, exists in Gastruloids. In a recent collaboration with @AlexandervanOu1
Group, we have probed this by performing scRNA seq go.nature.com/3d0lB6b

As all previous data suggests, gastruloids are similar to embryos at E8.0-E8.5 but here we can reveal the richness of cell types: endothelium, PGCs, neural crest, even placodal elements!

In addition to the de rigoeur scRNAseq we harnessed the power of the Tomoseq technique developed by the @AlexandervanOu1lab (bit.ly/2vmjCrO) to test the spatial organization of global gene expression.