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Cambridge Reproduction

 

As cells proceed through development, information contained in the genome is expressed in a context-dependent manner. This must be regulated precisely in both space and time to generate patterns of gene expression that set-up the spatial coordinates of tissue and organ primordia that build the embryo. Our current understanding of pattern formation relies on the concept of positional information, the idea that cells receive instructive signals that impart a spatial coordinate system to generate pattern. While this model works very well in static cell populations with minimal cell rearrangement, it becomes challenging when considering dynamic morphogenetic processes such as gastrulation. Furthermore, pattern formation in gastrulation is highly flexible to alterations in the size, scale and spatial rearrangement of cells in both experimental and evolutionary situations.

Our work seeks to provide illustrations of two concepts that will help resolve these long-standing problems of pattern regulation, evolvability and self-organisation. Firstly, downward causation emphasises the role that multi-tissue interactions play in relaying information from changes at the organ and organism level to the regulation of gene regulatory networks (GRNs) at the cell level. Secondly, pattern emergence considers how extracellular signals act to control the dynamics of autonomous GRN activity, rather than as instructive signals to direct cell fate transitions. In this sense, we propose that pattern formation should not be seen as a downstream output of organisers and their responding tissues, but rather as an emergent property of their dynamic interaction. How cells integrate this information with changes in the availability and uptake of nutrients is a current focus of our research.

Benjamin Steventon

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