Distinct but overlapping expression patterns of members of the Ikaros gene family during hematopoiesis might result in the formation of different multimeric complexes that have specific roles in lineage progression. The preferential expression of Helios in the earliest stages of hematopoiesis suggests that this gene functions predominantly in early progenitors.
In an expression screen for factors that pattern or induce ventral mesoderm, we isolated a complementary DNA encoding Mix.1, a paired class homeobox gene with no previously known function. Injection of Mix.1 messenger RNA results in extensive blood formation in the whole embryo and transforms dorsal mesoderm to a ventral fate. Mix.1 expression is induced by bone morphogenetic protein-4 (BMP-4), and a dominant inhibitory mutant of Mix.1 can restore a dorsal axis in embryos ventralized by ectopic BMP-4 expression. Mix.1 can form heterodimers with the dorsalizing gene siamois, which encodes a homeodomain protein that is structurally similar to Mix.1. Furthermore, Mix.1 blocks the duplicated axis induced by ectopic siamois expression. Our findings indicate that Mix.1 participates in a BMP-4 signalling pathway to pattern ventral mesoderm, and suggest a model whereby dimerization of homeodomain proteins regulates dorsal-ventral patterning.
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