MOLECULAR CONTROL OF HAEMOGENIC ENDOTHELIUM FATE

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During embryonic life, the blood system is established in successive waves from specialized endothelial subsets. The generation of blood cells from these endothelial subsets is carefully timed and coordinated to provide the growing embryo with specific blood cell types that are needed at each successive stage of development. The molecular mechanism that regulates when these subsets of specialized endothelial give rise to blood cells is still poorly understood.In the present project, we will aim to determine the underlying molecular mechanism that controls how these endothelium subsets are temporally maintained or how they are instructed by external stimuli to generate blood cells. In this context, we will explore the interaction between two transcriptional regulators, one controlling the endothelial programme and one controlling the blood programme. We hypothesise that the interaction between these two regulators of gene expression is critical to control the timing of blood cell generation during embryonic development. To address these questions, we will use an experimental system based on mouse embryonic stem cells that mimics normal development in vitro and in which we can easily manipulate gene expression and generate enough cells to examine many different features. Using fluorescent reporter proteins, we will follow the expression of these two transcriptional regulators and we will also determine how these two regulators interact with each other. Our work will answer a number of fundamental questions on how blood cell emergence is controlled at the molecular level during embryonic development.