Development of cmyb-independent macrophages from the primitive hematopoiesis

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In order to understand the role of tissue macrophages in homeostasis and disease, we have to analyze and identify the embryonic origin of these important immune cells. Recently, it was reported that two subpopulations of tissue macrophages, originating from primitive and definitive hematopoiesis, exist next to each other in adult organs. Whereas essential factors for the differentiation of myeloid cells from the definitive hematopoiesis are well defined, there is only scarce knowledge about factors guiding primitive myelopoiesis in the yolk sac.In the following research project I want to address basic and essential questions regarding the primitive hematopoiesis and the origin of cmyb-independent macrophages.I want to define exogenous and endogenous factors essential for the primitive hematopoiesis in the yolk sac. Key factors of the stromal compartment required for the induction of macrophages will be identified and characterized first. This will provide evidence whether the key factors for macrophage development in the yolk sac are identical or different to those in the fetal liver or in the adult bone marrow. Furthermore, a detailed characterization of the different myeloid progenitors of the cmyb independent tissue macrophages will define which specific surface molecules are expressed on these cells. With these data available a lineage specific marker might be identified to identify, trace and target cmyb-independent macrophages.In the next step I want to follow the migration routes and characterize the distribution of tissue macrophages from the yolk sac, clarifying the order of colonization during embryonic development. Finally I want to analyze the presumably different functions of cmyb-dependent and cmyb-independent tissue macrophages in homeostasis and inflammation in an animal model of metabolic syndrome. With these results available we will gain a deeper insight into the origin and function of cmyb-independent tissue macrophages, leading to a better understanding on the role of these unique cells in physiological and pathophysiological settings.