Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development

Blood development, or hematopoiesis, is an evolutionarily conserved process that is essential to life in many organisms. The hematopoetic development of Drosophila melanogaster is an effective genetic and functional model of the myeloid lineage of vertebrate hematopoiesis, due to conserved signaling pathways and transcription factors dictating cell proliferation and differentiation. In both vertebrate and Drosophila hematopoiesis, the differentiated blood cells, or hemocytes, form from a common hematopoietic precursor cell. Both the hematopoietic stem cells (HSCs) in vertebrates, and the hemocyte progenitors in Drosophila, asymmetrically divide into one pluripotent stem cell and one cell that has been committed to a path of differentiation. Two genes whose functions have been studied in the differentiation of germline stem cells of Drosophila, bag-of-marbles (bam) and zero population growth (zpg), and have been found by our lab to be necessary for normal larval hematopoiesis. Preliminary data I have collected from a sensitized genetic screen suggest that a negative regulator of translational initiation, NAT1 (N-Acetyltransferase 1), may be necessary for proper Bam function in the larval lymph gland. In addition, phenotypic analysis of zpg homozygous null mutants and zpg RNAi knockdown suggest that zpg is necessary for proper differentiation of mature crystal cells and it represses lamellocyte fate in the hematopoietic organ, the lymph gland (LG). Though bam and zpg were originally thought to be specific to the germline, we hypothesize that these and other factors involved in germline stem cell maintenance and differentiation may also be important in hematopoietic progenitor maintenance and differentiation.