IPLS/BioP Seminar: Dr. Berta Verd (University of Oxford)

Abstract: Pattern formation emerges during development from the interplay between gene regulatory networks (GRNs) acting at the single cell level and cell movements driving tissue level morphogenetic changes. As a result, the timing of cell specification and the dynamics of morphogenesis must be tightly cross-regulated. In the developing zebrafish, mesoderm progenitors will spend varying amounts of time in the tailbud before entering the pre-somitic mesoderm (PSM) and initiating a stereotypical transcriptional trajectory towards a mesodermal fate. In contrast, when dissociated and placed in vitro, these progenitors differentiate synchronously roughly with the same dynamics as the fastest differentiating cell in vivo. We have used a data-driven mathematical modelling approach to reverse-engineer a GRN that is able to tune the timing of mesodermal differentiation as progenitors leave the tailbud’s signalling environment, which also explains the in vitro observations. This GRN is also able to recapitulate pattern emergence at the tissue level when modelled on cell tracks obtained from live-imaging a developing PSM; a methodology that we have named “live-modelling”. Modelling pattern formation in this way has revealed previously uncharacterized sources of noise across expression boundaries, predicting that it might be an emergent property of the network's memory and the differential antero-posterior cell motility across the PSM. This framework has made it possible to - for the first time -  study developmental pattern emergence on a realistic representation of the underlying morphogenetic scenario and, will ultimately help build a mechanistic understanding of how developmental processes evolve.  

Host: Buzz Baum

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