title: The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction.
abstract: Wnt signalling is required for neural crest (NC) induction; however, the direct targets of the Wnt pathway during NC induction remain unknown. We show here that the homeobox gene Gbx2 is essential in this process and is directly activated by Wnt/beta-catenin signalling. By ChIP and transgenesis analysis we show that the Gbx2 regulatory elements that drive expression in the NC respond directly to Wnt/beta-catenin signalling. Gbx2 has previously been implicated in posteriorization of the neural plate. Here we unveil a new role for this gene in neural fold patterning. Loss-of-function experiments using antisense morpholinos against Gbx2 inhibit NC and expand the preplacodal domain, whereas Gbx2 overexpression leads to transformation of the preplacodal domain into NC cells. We show that the NC specifier activity of Gbx2 is dependent on the interaction with Zic1 and the inhibition of preplacodal genes such as Six1. In addition, we demonstrate that Gbx2 is upstream of the neural fold specifiers Pax3 and Msx1. Our results place Gbx2 as the earliest factor in the NC genetic cascade being directly regulated by the inductive molecules, and support the notion that posteriorization of the neural folds is an essential step in NC specification. We propose a new genetic cascade that operates in the distinction between anterior placodal and NC territories.
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Sei
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Mauricio
authors.initials: M
authors.lastname: Moreno
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495266:CTNNB1 protein, Xenopus; D017931:DNA Primers; C513180:Gbx2 protein, Xenopus; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; C116546:Zic1 protein, Xenopus; D051176:beta Catenin