The transcription factor Vox represses endoderm development by interacting with Casanova and Pou2
- Authors
- Zhao, J., Lambert, G., Meijer, A.H., and Rosa, F.M.
- ID
- ZDB-PUB-130211-10
- Date
- 2013
- Source
- Development (Cambridge, England) 140(5): 1090-1099 (Journal)
- Registered Authors
- Lambert, Guillaume, Meijer, Annemarie H., Rosa, Frederic, Zhao, Jue
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/metabolism
- Bone Morphogenetic Proteins/physiology
- Down-Regulation/genetics
- Embryo, Nonmammalian
- Endoderm/embryology*
- Endoderm/growth & development
- Endoderm/metabolism
- Gene Expression Regulation, Developmental
- Homeodomain Proteins/chemistry
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Homeodomain Proteins/physiology*
- Nodal Signaling Ligands/genetics
- Nodal Signaling Ligands/metabolism
- Nodal Signaling Ligands/physiology
- Octamer Transcription Factor-3/metabolism*
- Octamer Transcription Factor-3/physiology
- Protein Binding/physiology
- Protein Interaction Domains and Motifs/genetics
- Protein Interaction Domains and Motifs/physiology
- Repressor Proteins/chemistry
- Repressor Proteins/genetics
- Repressor Proteins/metabolism*
- Repressor Proteins/physiology*
- SOX Transcription Factors/metabolism*
- SOX Transcription Factors/physiology
- Sequence Deletion
- Tissue Distribution
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Transcription Factors/physiology
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Zebrafish Proteins/physiology*
- PubMed
- 23364327 Full text @ Development
Endoderm and mesoderm are both formed upon activation of Nodal signaling but how endoderm differentiates from mesoderm is still poorly explored. The sox-related gene casanova (sox32) acts downstream of the Nodal signal, is essential for endoderm development and requires the co-factor Pou2 (Pou5f1, Oct3, Oct4) in this process. Conversely, BMP signals have been shown to inhibit endoderm development by an as yet unexplained mechanism. In a search for Casanova regulators in zebrafish, we identified two of its binding partners as the transcription factors Pou2 and Vox, a member of the Vent group of proteins also involved in the patterning of the gastrula. In overexpression studies we show that vox and/or Vent group genes inhibit the capacity of Casanova to induce endoderm, even in the presence of its co-factor Pou2, and that Vox acts as a repressor in this process. We further show that vox, but not other members of the Vent group, is essential for defining the proper endodermal domain size at gastrulation. In this process, vox acts downstream of BMPs. Cell fate analysis further shows that Vox plays a key role downstream of BMP signals in regulating the capacity of Nodal to induce endoderm versus mesoderm by modulating the activity of the Casanova/Pou2 regulatory system.