Conserved Role of FoxH1 in Early Differentiation Processes

During development the fertilized egg divides many times and many different types of cells must form. To end up in a multicellular organism many differentiation processes and many different signaling pathways are involved. This happens through the tightly regulated expression of different genes, which involves protein switches called transcription factors (TFs). TFs recognize and attach to specific parts of the DNA to turn on or off their target genes. In recent years scientists are focusing more on how the 3D architecture of the larger DNA structures, called chromosomes, changes gene expression. During this project, the transcription factor FoxH1 will be investigated. FoxH1 is a TF within the Nodal- signaling pathway, through which cells communicate with each other during early development. In particular, division of the embryo into the different tissue layers, endoderm and mesoderm, depends on this pathway. To fulfil its function, the FoxH1 protein binds to different DNA sequences. Research shows that FoxH1 not only regulates gene activation in the typical way, but that it also influences chromosomal architecture. In our study, different model systems will be used to clarify how FoxH1 acts in early differentiation and in mesoderm development in particular. It is hypothesized that FoxH1 binds close to, as well as far away from, genes that it is regulating. This leads to folding of the chromosome, which directly influences gene expression. Different molecular biological methods will be used to identify and confirm genes which are regulated by FoxH1 in a classical manner or via chromatin folding events. Their impact on early development and cell differentiation processes will be analysed, as well as the influence of FoxH1 on chromosomal architecture. In the long term, the generated data and findings will be applied for further investigations on TFs of the Nodal-signaling pathway. This includes the establishment of a detailed network of the early cell differentiation.