Speaker Dr Caroline Hill, Assistant Research Director and Principal Group Leader, The Francis Crick Institute

Title How the zebrafish makes its guts

Host Fiona Wardle

 

Abstract Specification of the three germ layers in early embryogenesis by graded Nodal signalling is frequently regarded as a paradigm for patterning through a single morphogen gradient, with endoderm presumed to require high levels of Nodal signalling, whilst mesoderm specification requires lower levels. However, by exploiting the unique properties of the zebrafish embryo to visualise the dynamics of signalling and cell fate allocation, we have demonstrated that Nodal functions with FGF to determine the pattern of endoderm and mesoderm specification. We have gone on to determine how endoderm progenitors are specified in a ‘salt and pepper’ pattern within the first two cell tiers of the zebrafish embryo, interspersed with mesoderm progenitors. We have shown that Nodal signalling gives rise to a population of bipotential progenitors, and then during a short competency window of about 1 hour before the cells start to involute, a subset of these bipotential progenitors within the first two cell tiers stochastically switch to an endodermal cell fate, with the rest of the population being specified as mesoderm. Switching requires inhibition of FGF/ERK signalling. We have very recently discovered the origin of heterogeneity in the FGF/ERK signalling pathway, which results in windows of ERK inactivity. This will be discussed further in the seminar.