Primitive erythropoiesis in the Xenopus embryo: the synergistic role of LMO-2, SCL and GATA-binding proteins

Hematopoietic stem cells are derived from ventral mesoderm during vertebrat e development. Gene targeting experiments in the mouse have demonstrated ke y roles for the basic helix-loop-helix transcription factor SCL and the GAT A-binding protein GATA-1 in hematopoiesis. When overexpressed in Xenopus an imal cap explants, SCL and GATA-1 are each capable of specifying mesoderm t o become blood. Forced expression of either factor in whole embryos, howeve r, does not lead to ectopic blood formation. This apparent paradox between animal cap assays and whole embryo phenotype has led to the hypothesis that additional factors are involved in specifying hematopoietic mesoderm, SCL and GATA-1 interact in a transcriptional complex with the LIM domain protei n LMO-2, We have cloned the Xenopus homolog of LMO-2 and show that it is ex pressed in a similar pattern to SCL during development. LMO-2 can specify h ematopoietic mesoderm in animal cap assays. SCL and LMO-2 act synergistical ly to expand the blood island when overexpressed in whole embryos. Furtherm ore, co-expression of GATA-1 with SCL and LMO-2 leads to embryos that are v entralized and have blood throughout the dorsal-ventral axis, The synergist ic effect of SCL, LMO-2 and GATA-1, taken together with the findings that t hese factors can form a complex in vitro, suggests that this complex specif ies mesoderm to become blood during embryogenesis.