d-Asb11 is an essential mediator of canonical Delta-Notch signalling

Sander H. Diks, Maria A. Sartori da Silva, Jan Luuk Hillebrands, Robert J. Bink, Henri H. Versteeg, Carina Van Rooijen, Anke Brouwers, Ajay B. Chitnis, Maikel P. Peppelenbosch*, Danica Zivkovic

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1190-1198
Number of pages9
JournalNature Cell Biology
Volume10
Issue number10
DOIs
Publication statusPublished - 2008
Externally publishedYes

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