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.
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
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes