| Hematopoiesis involves the specification of distinct cell fates from a pool of equivalent progenitors. Multiple signaling pathways have been implicated in the maintenance of pluripotent hematopoietic stem cells (HSCs) and their progressive differentiation into distinct cell fates. The commitment of progenitors along specific hematopoietic lineages involves complex transcriptional regulation by both general and lineage-specific transcription factors, and the inactivation or aberrant regulation of these transcription factors frequently results in leukemias.; Here we describe multiple molecular relationships involved in the specification of Drosophila hemocyte lineages. In Drosophila hematopoiesis, two major distinct classes of cells observed are plasmatocytes and crystal cells. We have characterized the expression and function of Lozenge, (Lz), a Runt Domain transcription factor that bears homology to human AML1 (Acute Myeloid Leukemial), in the development of crystal cells during embryonic and larval hematopoietic development. Another transcription factor, Glial Cells Missing (Gcm), has previously been shown to be required for plasmatocyte development. The misexpression of Gcm in the crystal cell precursors results in the transformation of the crystal cells into plasmatocytes. The Drosophila GATA protein, Serpent (Srp) is required for both Lz and Gcm expression and is required for development of both plasmatocytes and crystal cells, whereas Lz and Gcm are required in a lineage-specific manner.; Differentiation of hemocytes is also observed in the lymph glands, and a role for the Notch pathway in the specification of the crystal cell lineage is described. Lz expression and crystal cell development is absent in Serrate (Ser), Notch ( N), and suppressor of Hairless (su( H)) mutant lymph glands. Serrate is expressed in the lymph glands, and is observed in close but non-overlapping proximity to Lz+ cells, possibly suggesting an inductive relationship. Given the similarities of Srp and Lz to GATA and AML1 proteins, and a repeated role for Notch and Serrate in hematopoiesis, these studies point to evolutionarily conserved molecular mechanisms in blood development, and are likely to have broad implications for our understanding of mammalian hematopoiesis and leukemias. |
