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

了解脊椎动物胚胎中神经细胞产生的分子机制有助于深入了解胚胎干细胞在培养中产生神经细胞过程中必须发生的关键步骤。我们最近表明，两种关键细胞信号(成纤维细胞生长因子和维生素A的衍生物维甲酸)之间的切换控制着神经细胞产生的开始。我们计划建立在这一发现和新数据的基础上，这些数据表明，细胞分裂时间的变化和基因对调控信号的可及性的变化可能是由这种信号开关控制的重要步骤。这些细胞周期时间和基因可及性变化的调节和后果将在鸡和小鼠胚胎中进行详细研究。我们还计划进行一项筛选，以确定受这一信号开关调控的基因表达的进一步变化。这项工作将有助于我们对神经分化的分子基础的基本理解。它还将为指导胚胎干细胞产生稳定神经元的方案提供信息，从而有助于开发治疗神经损伤或疾病的疗法。

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.