BMP-4-RESPONSIVE REGULATION OF DORSAL-VENTRAL PATTERNING BY THE HOMEOBOX PROTEIN MIX.1

IN an expression screen for factors that pattern or induce ventral mes oderm, we isolated a complementary DNA encoding Mix.1, a paired class homeobox gene, with no previously known function(1). Injection of Mix. 1 messenger RNA results in extensive blood formation in the whole embr yo and transforms dorsal mesoderm to a ventral fate. Mix.1 expression is induced by bone morphogenetic protein-4 (BMP-4), and a dominant inh ibitory mutant of Mix.1 can restore a dorsal axis in embryos ventraliz ed by ectopic BMP-4 expression. Mix.1 can form heterodimers uith the d orsalizing gene siamois, which encodes a homeodomain protein that is s tructurally similar to Mix.1. Furthermore, Mix.1 blocks the duplicated axis induced by ectopic siamois expression. Our findings indicate tha t Mix.1 participates in a BMP-4 signalling pathway to pattern ventral mesoderm, and suggest a model whereby dimerization of homeodomain prot eins regulates dorsal-ventral patterning.