Hematopoiesis is, in part, regulated by direct cell-to-cell contact between developing blood cells and non-hematopoietic stromal cells. Stromal cells, through their elaboration of an extracellular milieu, promote cellular recognition, adhesion, and proliferation of a given line of blood cells. The nature of the extracellular components and their roles in hematopoiesis are largely unknown. Therefore, the proposed study will combine ultrastructural, histochemical, and biochemical work to study extracellular components shown to have regulatory functions in other developing systems. Glycosaminoglycans and sialic acid will be identified and quantitated in hematopoietic regions using quantitative histochemical and biochemical studies. Intracellular junctions will be located and their nature determined in freeze-fracture studies. The developmental regulation of lectins will be determined through histochemical, immunocytochemical, and biochemical analysis. Chick embryos will be used for all of these studies because the segregation of their marrow into topologically distinct erythropoietic and granulopoietic compartments will facilitate differential analysis of the role of extracellular components. Specific strains of avian leukemia viruses are available to make either erythropoietic or granulopoietic compartments hyperplastic. These studies will therefore increase our understanding of how basic developmental events operate in hematopoiesis and how blood-stromal cell interactions are affected by leukemic transformations. Avian hematopoiesis is sufficiently similar to its mammalian counterpart that the information derived from these studies can be applied to furthering our knowledge of how human hematopoiesis operates in normal and leukemic states.
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