The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction
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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/β-catenin signalling. By ChIP and transgenesis analysis we show that the Gbx2 regulatory elements that drive expression in the NC respond directly to Wnt/β-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.
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gbx2 is known to have several roles in the embryo and is an early specifier of posterior neural crest in Xenopus.
“Known to have several roles in the embryo and an early specifier of posterior neural crest in Xenopus”
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- Authors
- Li, B., Kuriyama, S., Moreno, M., & Mayor, R.
- Affiliations
- University College London (GB)
- Corresponding author
- Mayor, Roberto
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-10-01
- Volume
- 136
- Issue
- 19
- Pages
- 3267-3278
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2808295
- OpenAlex
- W1974648749
- Cited by
- 149
- References
- 0
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 9 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 7 · 2014: 12 · 2013: 13 · 2012: 15
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Gbx2, Wnt/β-catenin signaling, neural crest induction, neural crest specification, posteriorization, ZIC1, Six1, Pax3, MSX1, homeobox genes, chick embryo
- MeSH terms
- Animals, Base Sequence, Binding Sites, Enhancer Elements, Genetic, Genes, Homeobox, Models, Biological, Molecular Sequence Data, Neural Crest, RNA, Messenger, Transcription Factors, Xenopus, Signal Transduction, DNA Primers, Homeodomain Proteins, Body Patterning, Xenopus Proteins, Animals, Genetically Modified, Wnt Proteins, beta Catenin
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