title: Essential and opposing roles of zebrafish beta-catenins in the formation of dorsal axial structures and neurectoderm.
abstract: In Xenopus, Wnt signals and their transcriptional effector beta-catenin are required for the development of dorsal axial structures. In zebrafish, previous loss-of-function studies have not identified an essential role for beta-catenin in dorsal axis formation, but the maternal-effect mutation ichabod disrupts beta-catenin accumulation in dorsal nuclei and leads to a reduction of dorsoanterior derivatives. We have identified and characterized a second zebrafish beta-catenin gene, beta-catenin-2, located on a different linkage group from the previously studied beta-catenin-1, but situated close to the ichabod mutation on LG19. Although the ichabod mutation does not functionally alter the beta-catenin-2 reading frame, the level of maternal beta-catenin-2, but not beta-catenin-1, transcript is substantially lower in ichabod, compared with wild-type, embryos. Reduction of beta-catenin-2 function in wild-type embryos by injection of morpholino antisense oligonucleotides (MOs) specific for this gene (MO2) results in the same ventralized phenotypes as seen in ichabod embryos, and administration of MO2 to ichabod embryos increases the extent of ventralization. MOs directed against beta-catenin-1 (MO1), by contrast, had no ventralizing effect on wild-type embryos. beta-catenin-2 is thus specifically required for organizer formation and this function is apparently required maternally, because the ichabod mutation causes a reduction in maternal transcription of the gene and a reduced level of beta-catenin-2 protein in the early embryo. A redundant role of beta-catenins in suppressing formation of neurectoderm is revealed when both beta-catenin genes are inhibited. Using a combination of MO1 and MO2 in wild-type embryos, or by injecting solely MO1 in ichabod embryos, we obtain expression of a wide spectrum of neural markers in apparently appropriate anteroposterior pattern. We propose that the early, dorsal-promoting function of beta-catenin-2 is essential to counteract a later, dorsal- and neurectoderm-repressing function that is shared by both beta-catenin genes.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, 19104, USA.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Bellipanni
authors.forename: Máté
authors.initials: M
authors.lastname: Varga
authors.forename: Shingo
authors.initials: S
authors.lastname: Maegawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Christina
authors.initials: C
authors.lastname: Kelly
authors.forename: Andrea Pomrehn
authors.initials: AP
authors.lastname: Myers
authors.forename: Felicia
authors.initials: F
authors.lastname: Chu
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
authors.forename: Eric S
authors.initials: ES
authors.lastname: Weinberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes; D003198:Computer Simulation; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D016678:Genome; D008845:Microinjections; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020897:Organizers, Embryonic / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins; D051176:beta Catenin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D005819:Genetic Markers; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D051176:beta Catenin