title: Xiro-1 controls mesoderm patterning by repressing bmp-4 expression in the Spemann organizer.
abstract: The Iroquois genes code for homeodomain proteins that have been implicated in the neural development of Drosophila and vertebrates. We show here for the first time that Xiro-1, one of the Xenopus Iroquois genes, is expressed in the Spemann organizer from the start of gastrulation and that its overexpression induces a secondary axis as well as the ectopic expression of several organizer genes, such as chordin, goosecoid, and Xlim-1. Our results also indicate that Xiro-1 normally functions as a transcriptional repressor in the mesoderm. Overexpression of Xiro-1 or a chimeric form fused to the repressor domain of Engrailed cause similar phenotypes while overexpression of functional derivatives of Xiro-1 fused with transactivation domains (VP16 or E1A) produce the opposite effects. Finally, we show that Xiro-1 works as a repressor of bmp-4 transcription and that its effect on organizer development is dependent on BMP-4 activity. We propose that the previously observed down regulation of bmp-4 in the dorsal mesoderm during gastrulation can be explained by the repressor activity of Xiro-1 described here. Thus, Xiro-1 seems to have at least two different functions: control of neural plate and organizer development, both of which could be mediated by repression of bmp-4 transcription.
authors.affiliation: Millennium Nucleus in Developmental Biology, Laboratory of Developmental Biology, Faculty of Science, University of Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Glavic
authors.forename: J L
authors.initials: JL
authors.lastname: Gómez-Skarmeta
authors.forename: R
authors.initials: R
authors.lastname: Mayor
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000502:physiology; D008648:Mesoderm / Q000502:physiology*; D009419:Nerve Tissue Proteins; D020897:Organizers, Embryonic / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C110460:IRX2 protein, Xenopus; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C484675:Xiro1 protein, Xenopus; C525812:bmp4 protein, Xenopus