The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms -intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r ΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r ΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r −/− rodents. Csf1r ΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.

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The process of T-lymphocyte differentiation within the thymus involves a series of molecular interactions. In this work we have carried out an analysis of the chick thymus microenvironment in order to evaluate its heterogeneity during development. We have produced 11 monoclonal antibodies whose staining patterns detected by the immunoperoxidase technique allowed us to divide them into five groups. A first group (E19-E2, P0-E5, and P15-T1) binds to thymic medullary stroma showing a reticular pattern on medullary epithelial cells and whose significance would be related to thymic stromal secretion. The second group of monoclonal antibodies (P15-T3) stains thymic corpuscles of 10- and 15-day chicks. The third group of antibodies includes P0-E1, P0-E3, P5-A6, and P15-T2 whose staining pattern is both medullary and cortical. The fourth group (P10-HB1 and P10-HB2) binds to thymic stromal and cortical thymocytes, and the fifth group (P5-A1) is characterized by the staining of medullary vessels of 5-day chicks. These five groups of monoclonal antibodies corroborate the existence of an antigenic diversity of the chick thymus microenvironment. Their possible relationships with T-cell differentiation and stromal-thymocyte interactions are discussed.

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