*4 Year WT Programme* Mechanisms regulating neural differentiation

Research in my group addresses cellular and molecular mechanisms that regulate neural differentiation using chick and mouse embryos as well as mammalian pluripotent stem cells. Understanding this process informs our ability to direct differentiation of neural tissue for therapeutic purposes following injury or disease.

Cell biological mechanisms regulating neuronal differentiation. We have developed novel real-time imaging approaches, which allow analysis of neuroepithelial cell behaviour during neurogenesis (Wilcock et al. 2007; Das et al. 2012) We have recently discovered that when a cell becomes a neuron it abscises its apical endfoot and that this involves regulated loss of apical polarity and dismantles a key signalling structure, the primary cilium (Das and Storey 2014). Projects would address the molecular mechanisms mediating this new form of cell sub-division. This would involve embryo/tissue manipulation, molecular biology, immunocytochemistry and fixed and live imaging approaches.

Signalling to chromatin. The signalling pathways that direct neural differentiation are now well known, but how these lead to coordinated expression of neural differentiation genes that constitute the neural programme is poorly understood. We discovered that opposition of fibroblast growth factor (FGF) and retinoid signalling controls neural differentiation onset in the elongating body axis (Diez del Corral et al. 2003) essentially, retinoid signalling rises during development and represses FGF signalling, driving differentiation (Stavridis et al. 2010). We have now shown that FGF acts by regulating accessibility (chromatin compaction) around neural differentiation gene loci (Patel et al. 2013). Projects would address the molecular pathway that links FGF to the regulation of higher order chromatin organisation and develop our ES cell neural differentiation assay. This would involve work with embryos, ES cells differentiation, molecular biology, immunocytochemistry and imaging approaches.