Xiro-1 controls mesoderm patterning by repressing bmp-4 expression in the Spemann organizer

The Iroquois genes code for homeodomain proteins that have been implicated in the neural development of Drosophila and vertebrates. We show here for t he 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 overex pression induces a secondary axis as well as the ectopic expression of seve ral organizer genes, such as chordin, goosecoid, and Xlim-1. Our results al so indicate that Xiro-1 normally functions as a transcriptional repressor i n the mesoderm. Overexpression of Xiro-1 or a chimeric form fused to the re pressor domain of Engrailed cause similar phenotypes while overexpression o f functional derivatives of Xiro-1 fused with transactivation domains (VP16 or E1A) produce the opposite effects. Finally, we show that Xiro-1 works a s a repressor of bmp-4 transcription and that its effect on organizer devel opment is dependent on BMP-4 activity. We propose that the previously obser ved down regulation of bmp-4 in the dorsal mesoderm during gastrulation can be explained by the repressor activity of Xiro-1 described here. Thus, Xir o-1 seems to have at least two different functions: control of neural plate and organizer development, both of which could be mediated by repression o f bmp-4 transcription. (C) 2001 Wiley-Liss, Inc.