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 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.
Mead
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PE
Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Brivanlou
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Kelley
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CM
Zon
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D000818:Animals; D019485:Bone Morphogenetic Proteins; D046508:Culture Techniques; D004625:Embryo, Nonmammalian / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D009024:Morphogenesis; D016296:Mutagenesis; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014981:Xenopus; D029867:Xenopus Proteins
D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C100368:Mix1 protein, Xenopus; D011506:Proteins; D012333:RNA, Messenger; C093133:SIA1 protein, Xenopus; D029867:Xenopus Proteins