PUBLICATION
SoxB1 transcription factors restrict organizer gene expression by repressing multiple events downstream of Wnt signalling
- Authors
- Shih, Y.H., Kuo, C.L., Hirst, C.S., Dee, C.T., Liu, Y.R., Laghari, Z.A., and Scotting, P.J.
- ID
- ZDB-PUB-100719-28
- Date
- 2010
- Source
- Development (Cambridge, England) 137(16): 2671-2681 (Journal)
- Registered Authors
- Shih, Yu-huan
- Keywords
- Sox3, Organizer, Wnt, bozozok (dharma), squint (ndr1), Zebrafish
- MeSH Terms
-
- Active Transport, Cell Nucleus
- Animals
- Animals, Genetically Modified
- Biomarkers/metabolism
- Gene Expression Regulation, Developmental*
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Mesoderm/metabolism
- Nodal Signaling Ligands/metabolism
- Protein Binding
- SOXB1 Transcription Factors/genetics
- SOXB1 Transcription Factors/metabolism*
- Signal Transduction*
- Transcription, Genetic
- Wnt Proteins/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 20610482 Full text @ Development
Citation
Shih, Y.H., Kuo, C.L., Hirst, C.S., Dee, C.T., Liu, Y.R., Laghari, Z.A., and Scotting, P.J. (2010) SoxB1 transcription factors restrict organizer gene expression by repressing multiple events downstream of Wnt signalling. Development (Cambridge, England). 137(16):2671-2681.
Abstract
Formation of the organizer is one of the most central patterning events in vertebrate development. Organizer-derived signals are responsible for establishing the CNS and patterning the dorsal ventral axis. The mechanisms promoting organizer formation are known to involve cooperation between Nodal and Wnt signalling. However, the organizer forms in a very restricted region, suggesting the presence of mechanisms that repress its formation. Here, we show in zebrafish that the transcription factor Sox3 represses multiple steps in the signalling events that lead to organizer formation. Although beta-catenin, Bozozok and Squint are known to play major roles in establishing the dorsal organizer in vertebrate embryos, overexpression of any of these is insufficient to induce robust expression of markers of the organizer in ectopic positions in the animal pole, where Sox3 is strongly expressed. We show that a dominant-negative nuclear localisation mutant of Sox3 can cause ectopic expression of organizer genes via a mechanism that activates all of these earlier factors, resulting in later axis duplication including major bifurcations of the CNS. We also find that the related SoxB1 factor, Sox19b, can act redundantly with Sox3 in these effects. It therefore seems that the broad expression of these SoxB1 genes throughout the early epiblast and their subsequent restriction to the ectoderm is a primary regulator of when and where the organizer forms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping