XIPOU 2 is a potential regulator of Spemann's Organizer.

XIPOU 2, a member of the class III POU-domain family, is expressed initially at mid-blastula transition (MBT) and during gastrulation in the entire marginal zone mesoderm, including Spemann's Organizer (the Organizer). To identify potential targets of XIPOU 2, the interaction of XIPOU 2 with other genes co-expressed in the Organizer was examined by microinjecting XIPOU 2's mRNA into the lineage of cells that contributes to the Organizer, head mesenchyme and prechordal plate. XIPOU 2 suppresses the expression of a number of dorsal mesoderm-specific genes, including gsc, Xlim-1, Xotx2, noggin and chordin, but not Xnot. As a consequence of the suppression of dorsal mesoderm gene expression, bone morphogenetic factor-4 (Bmp-4), a potent inducer of ventral mesoderm, is activated in the Organizer. Gsc is a potential target of XIPOU 2. XIPOU 2 is capable of binding a class III POU protein binding site (CATTAAT) that is located within the gsc promoter, in the activin-inducible (distal) element. Furthermore, XIPOU 2 suppresses the activation of the gsc promoter by activin signaling. At the neurula and tailbud stages, dorsoanterior structures are affected: embryos displayed micropthalmia and the loss of the first branchial arch, as detected by the expression of pax-6, Xotx2 and en-2. By examining events downstream from the Wnt and chordin pathways, we determined that XIPOU 2, when overexpressed, acts specifically in the Organizer, downstream from GSK-3beta of the Wnt pathway and upstream from chordin. The interference in dorsalizing events caused by XIPOU 2 was rescued by chordin. Thus, in addition to its direct neuralizing ability, in a different context, XIPOU 2 has the potential to antagonize dorsalizing events in the Organizer.