The role of the transcription factor Sp1 in embryonic macrophage development

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Macrophages are a type of white blood cell which are very important for the health of an organism. These cells have the ability to recognize infectious particles and send out alarm signals that mobilize the bodies? defenses. However, in the embryo they have different functions. Here they function mainly as scavengers and have the ability to ?eat? dead cells and cell debris, and therefore play important roles in shaping the body outline. For example, even in mammals hands are originally webbed and macrophages remove the skin between the fingers. In the project described here we wish to address the question how this cell type is formed in the embryo. All different cells of the organism originate from a single egg; the reason why they are all different is that they all express different sets of genes. Therefore we want to know which genes are responsible for generating embryonic macrophages. To find out which genes are responsible, we will use an embryonic stem (ES) cell line that lacks one specific protein (Sp1) that is responsible for the activity of many genes. We found that normal ES cells can be turned into embryonic macrophages by culturing them in special medium. However, in the absence of Sp1 these cells are not formed. When Sp1 is removed in mice, embryos are unable to develop. The reason for this is unclear, but our work suggests that macrophages may have something to do with it. Sp1 is a so-called transcription factor, which directly binds to the DNA of genes and switches them on. Very little is known about how and where it works. Using novel techniques we can identify all genes within the cell which are bound by Sp1 and we can then test whether they fail to be switched on in its absence. The final outcomes of this work will be (i) a list of genes of which we now know that they are important for forming macrophages, and (ii) a much more detailed understanding of how Sp1 acts in this process. This work is not only of relevance to macrophage biology but also to the understanding of embryogenesis as such.