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Bone morphogenetic protein-4 (BMP-4) has been shown as an essential factor in differentiation of the primitive blood cells in Xenopus laevis embryo. Organizer factors, in contrast, function as a negative regulator for the blood cell differentiation. Differentiation of both blood cells and muscle tissue are negatively regulated by the organizer activity. However, blood cells but not muscle tissue can differentiate in the organizer-depleted embryos produced by removal of vegetal cortex cytoplasm at the one-cell stage. Thus the blood cells are totally independent cells from the organizer activity. The down-stream target molecules of the BMP-4 signaling, such as vent-1/2 and msx-1/2 are the positive regulators for muscle tissue differentiation, whereas these factors do not promote blood cell formation. It has not yet been elucidated how the BMP-4 signaling promotes the differentiation of blood cells, but it is likely that transcription factors such as GATA-2, SCL, LMO-2, biklf and GATA-1 are at least involved in the initial blood program. Experiments using combined germ layer explants suggest that interaction between ectoderm and mesoderm at the gastrula stage is important for the blood cell formation in mesoderm. BMP-4 produced in the ectodermal cells is essential for this interaction. For understanding the whole program in the embryonic blood cell differentiation, it is important to elucidate the molecular mechanisms underlying the tissue-tissue interaction, in addition to the analysis of the regulatory cascade that takes place in the mesodermal cells.

Regulatory Signals and Tissue Interactions in the Early Hematopoietic Cell Differentiation in Xenopus laevis Embryo