Neural differentiation in ES cells

Embryonic stem cells are able to self renew indefinitely and in the right culture conditions can then undergo directed differentiation to give rise to specific cell types. We are investigating the requirement and mode of action of FGF and other signals during neural differentiation of ES cells.

Our work has shown that a discrete period of FGF signalling is required for the expression of markers of neural progenitors. These are cells that are specified to become part of the nervous system, but are still dividing, proliferative cells. Binding of FGF protein to its receptor on the cell surface can stimulate a number of 'chain reactions' or signalling pathways which relay the FGF signal to the cell nucleus, where changes in gene expression take place. We have found that one of these, the Erk1/2 /MAP kinase pathway, is specifically required for this neural specification step in embryos and in ES cells (Lunn et al. 2007;Stavridis et al. 2007). Our work has addressed how this signalling pathway promotes neural identity and how other pathways interact with Erk1/2 /MAP kinase during this process. Following exposure to FGF signalling for a defined period, however, attenuation of this pathway now promotes further differentiation (Starvidis et al 2010). Current work addresses how FGF signalling orchestrates differentiation progression by interacting with key regulators of chromatin organisation.