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.
Witta
S E
SE
Genetics and Biochemistry Branch, NIDDK, NIH, Bethesda, MD 20892-1766, USA.
Sato
S M
SM
D028341:Activins; D000818:Animals; D015415:Biomarkers; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D001757:Blastomeres / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis; D002454:Cell Differentiation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D005775:Gastrula / Q000166:cytology / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D007265:Inhibins / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D008845:Microinjections; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D050809:POU Domain Factors; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000008:administration & dosage / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D013489:Suppression, Genetic; D013623:Tail; D014157:Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D014981:Xenopus; D029867:Xenopus Proteins; D001616:beta-Galactosidase / Q000096:biosynthesis
D015415:Biomarkers; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D050809:POU Domain Factors; C490059:POU3F4 protein, Xenopus; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D028341:Activins; D007265:Inhibins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D001616:beta-Galactosidase