PUBLICATION
d-Asb11 is an essential mediator of canonical Delta-Notch signalling
- Authors
- Diks, S.H., Sartori da Silva, M.A., Hillebrands, J.L., Bink, R.J., Versteeg, H.H., van Rooijen, C., Brouwers, A., Chitnis, A.B., Peppelenbosch, M.P., and Zivkovic, D.
- ID
- ZDB-PUB-080915-2
- Date
- 2008
- Source
- Nature cell biology 10(10): 1190-1198 (Journal)
- Registered Authors
- Chitnis, Ajay, van Rooijen, Carina
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/metabolism
- Feedback, Physiological
- Genes, Reporter
- HeLa Cells
- Humans
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins/metabolism*
- Protein Binding
- Receptors, Notch/metabolism*
- Signal Transduction*
- Suppressor of Cytokine Signaling Proteins/metabolism*
- Transcriptional Activation/genetics
- Zebrafish/embryology
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 18776899 Full text @ Nat. Cell Biol.
Citation
Diks, S.H., Sartori da Silva, M.A., Hillebrands, J.L., Bink, R.J., Versteeg, H.H., van Rooijen, C., Brouwers, A., Chitnis, A.B., Peppelenbosch, M.P., and Zivkovic, D. (2008) d-Asb11 is an essential mediator of canonical Delta-Notch signalling. Nature cell biology. 10(10):1190-1198.
Abstract
In canonical Delta-Notch signalling, expression of Delta activates Notch in neighbouring cells, leading to downregulation of Delta in these cells. This process of lateral inhibition results in selection of either Delta-signalling cells or Notch-signalling cells. Here we show that d-Asb11 is an important mediator of this lateral inhibition. In zebrafish embryos, morpholino oligonucleotide (MO)-mediated knockdown of d-Asb11 caused repression of specific Delta-Notch elements and their transcriptional targets, whereas these were induced when d-Asb11 was misexpressed. d-Asb11 also activated legitimate Notch reporters cell-non-autonomously in vitro and in vivo when co-expressed with a Notch reporter. However, it repressed Notch reporters when expressed in Delta-expressing cells. Consistent with these results, d-Asb11 was able to specifically ubiquitylate and degrade DeltaA both in vitro and in vivo. We conclude that d-Asb11 is a component in the regulation of Delta-Notch signalling, important in fine-tuning the lateral inhibition gradients between DeltaA and Notch through a cell non-autonomous mechanism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping