title: Pygopus is required for embryonic brain patterning in Xenopus.
abstract: We have identified two Xenopus mRNAs that encode proteins homologous to a component of the Wnt/beta-catenin transcriptional machinery known as Pygopus. The predicted proteins encoded by both mRNAs share the same structural properties with human Pygo-2, but with Xpygo-2alpha having an additional 21 N-terminal residues. Xpygo-2alpha messages accumulate in the prospective anterior neural plate after gastrulation and then are localized to the nervous system, rostral to and including the hindbrain. Xpygo-2beta mRNA is expressed in oocytes and early embryos but declines in level before and during gastrulation. In late neurula, Xpygo-2beta mRNA is restricted to the retinal field, including eye primordia and prospective forebrain. A C-terminal truncated mutant of Xpygo-2 containing the N-terminal Homology Domain (NHD) caused both axis duplication when injected at the 2-cell stage and inhibition of anterior neural development when injected in the prospective head, mimicking the previously described effects of Wnt-signaling activators. Inhibition of Xpygo-2alpha and Xpygo-2beta by injection of gene-specific antisense morpholino oligonucleotides into prospective anterior neurectoderm caused brain defects that were prevented by coinjection of Xpygo-2 mRNA. Both Xpygo-2alpha and Xpygo-2beta morpholinos reduced the eye and forebrain markers Xrx-1, Xpax-6, and XBF-1, while the Xpygo-2alpha morpholino also eliminated expression of the mid-hindbrain marker En-2. The differential expression and regulatory activities of Xpygo-2alpha/beta in rostral neural tissue indicate that they represent essential components of a novel mechanism for Wnt signaling in regionalization of the brain.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, A1B 3V6 Newfoundland, Canada. f43bbl@mun.ca
authors.forename: Blue B
authors.initials: BB
authors.lastname: Lake
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Kao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D001921:Brain / Q000196:embryology*; D004247:DNA / Q000235:genetics; D005123:Eye / Q000196:embryology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D004247:DNA