Collaborating Investigators at Yale University School of Medicine have jointly devoted a Program Project on the molecular basis of myelopoiesis. The research themes focus on the identification and characterization of genes that are critical to the normal pathway of differentiation from the pluripotent hematopoietic stem cell, through intermediate progenitor and precursor cell stages, to mature differentiated and functional neutrophils. These themes coalesce in efforts to improve our understanding of the molecular anatomy of gene expression in myelopoiesis and the specific pathways that regulate the differentiation, maturation and function of myeloid cells. This Program Project is organized into a team approach for the integrated pursuit of four research projects supported by one technical core and one administrative core. The individual projects address the characterization of the role and function of a homeobox gene (Pitx2) that is preferentially expressed in primitive hematopoietic stem cells; characterization of transcription factors and genetic sequences required for the cell-type specific expression of the cell surface antigen CD34 in early hematopoiesis; characterization of the molecular basis for the block in stem cell differentiation that is associated with myeloid leukemia, and characterization of the changes in gene expression that occur with activation of mature neutrophils. The technical core will provide the following state- of-the-art services to the projects: protein purification, protein expression analysis and gene expression analysis. This Program Project application brings together investigators from four different departments of the institution, with a wide variety of basic research expertise to address a number of important questions in hematopoiesis.