Publication

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

Diks, S. H., da Silva, M. A. S., Hillebrands, J-L., Bink, R. J., Versteeg, H. H., van Rooijen, C., Brouwers, A., Chitnis, A. B., Peppelenbosch, M. P. & Zivkovic, D., Oct-2008, In : Nature Cell Biology. 10, 10, p. 1190-1198 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

In canonical Delta-Notch signalling, expression of Delta activates Notch in neighbouring cells, leading to of Delta in these cells(1). 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
Publication statusPublished - Oct-2008

    Keywords

  • UBIQUITIN LIGASE, CELL FATE, MIND BOMB, ZEBRAFISH, DROSOPHILA, ENDOCYTOSIS, PATHWAY, PROTEIN, GENE, NRARP

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