Cell cycle and epigenetic changes during neural differentiation in vertebrate embryos and ES cells

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Understanding the molecular mechanisms that underlie the generation of nerve cells in the vertebrate embryo provides insight into the key steps that must take place during the production of nerve cells from embryonic stem cells in culture.We have shown recently that a switch between two key cell signals (Fibroblast growth factor and Retinoic acid, a derivative of Vitamin A) controls the onset of nerve cell production. We plan to build on this discovery and on new data which indicate that changes in the time a cell takes to divide and in the accessibility of genes to regulatory signals may be important steps that are controlled by this signal switch. The regulation and consequences of these changes in cell cycle time and gene accessibility will be investigated in detail in chick and mouse embryos. We also plan to carry out a screen to identify further changes in gene expression regulated by this signal switch. This work will contribute to our basic understanding of the molecular basis of neural differentiation. It will also inform protocols for directing stable neuron production in embryonic stem cells and therefore help to develop therapies for treatment of neural injury or disease.