(A) The clo gene product and fli1 function at the top of the hierarchal cascade to drive formation of the hemangioblast from mesoderm precursors. The hemangioblast subsequently gives rise to hematopoietic progenitors expressing gata2, lmo2 and scl. Expression of gata2 and lmo2 is independent of gfi1aa expression, while gfi1aa is required for scl expression, and vice-versa. Primitive hematopoietic progenitors expressing lmo2, scl and gfi1aa generate erythroid and myeloid progenitors, regulated by gata1 and pu.1, respectively. gata1 and pu.1 antagonize each other to specify erythroid vs. myeloid progenitor commitment. Downstream in the primitive wave, gata1 is required for gfi1b expression. (B) In definitive hematopoiesis, runx-1, c-myb, ikaros and gfi1b act in parallel to specify definitive HSC and subsequently drive formation of downstream definitive lineages marked by globin (erythrocytes), cd41 (thrombocytes) and rag-1 (lymphocytes).