How can we understand pattern formation in embryo development when so much cell movement is happening at the same time? We studied how domains of T-box expression form within zebrafish presomitic mesoderm- and actively converging and extension tissue
http://shorturl.at/guwL3 

We first estimated the range of differentiation trajectories cells can take as they move from a posterior tbxta positive stage into a tbx24 positive PSM state. To generate an expression pattern, cells must somehow tune these dynamics to appropriately couple with cell movements.

We then fit parameters of a gene regulatory network which delayed the onset of differentiation to the range of observed differentiation time-scales, and adjusted their Wnt and FGF input accordingly.

Our model predicted that cells should differentiate synchronously once a low threshold of FGF activity has been reached- something we then observe in vitro.

So, how does this system then achieve the full range of dynamic profiles in vivo? This is required to form expression domains. We hypothesise that cell movements themselves may be playing a role.

Using tracking data from multiphoton movies we, for the first time, model GRNs on real biological tracks, with signalling as an input parameter. We see our model maintains gene expression domains very similar to those in vivo #LiveModelling

We notice posterior heterogeneity of gene expression in simulations, and also find these erroneously expressing cells. We see incorrect gene expression correlates with anterior-posterior movement of cells. A conclusion we would never have found without modelling on tracking data

Therefore, cell movements are a key component to regulate GRN dynamics through the movement of cells towards or away from signalling sources and sinks. This may ensure robust differentiation in the formation of somites whilst also permitting whole embryonic axis elongation.

Further investigation will be key in order to improve our understanding of how gene expression patterns emerge within developing multi-cellular systems, and will help identify which control parameters....

.....at various levels of biological organisation, must be modified in order to reliably bioengineer organoids for therapeutic applications

More on this idea from @Larabeeee https://www.preprints.org/manuscript/202006.0168/v1

A big thank you to everyone who worked on this project @CamMicroscopy @GeneticsCam @BertaVerd @hwang_seongwon @LewisThomson13 @_Bethan_Clark @BenSteventon2 and those who funded it, and supported the many summer students involved @Catz_Cambridge @Kings_College