Abstract
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 language | English |
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Pages (from-to) | 1190-1198 |
Number of pages | 9 |
Journal | Nature Cell Biology |
Volume | 10 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct-2008 |
Keywords
- UBIQUITIN LIGASE
- CELL FATE
- MIND BOMB
- ZEBRAFISH
- DROSOPHILA
- ENDOCYTOSIS
- PATHWAY
- PROTEIN
- GENE
- NRARP