Letter abstract
Nature Cell Biology 10, 1190 - 1198 (2008)
Published online: 7 September 2008 | doi:10.1038/ncb1779
d-Asb11 is an essential mediator of canonical Delta–Notch signalling
Sander H. Diks1, Maria A. Sartori da Silva1,2, Jan-Luuk Hillebrands1, Robert J. Bink2, Henri H. Versteeg1, Carina van Rooijen2, Anke Brouwers2, Ajay B. Chitnis3, Maikel P. Peppelenbosch1 & Danica Zivkovic2
In canonical Delta–Notch signalling, expression of Delta activates Notch in neighbouring cells, leading to downregulation of Delta in these cells1. 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.
- Deptartment of Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, NL-9713 AV Groningen, The Netherlands.
- Hubrecht Institute, Developmental Biology and Stem Cell Research, Uppsalalaan 8, NL-3584 CT Utrecht, The Netherlands.
- Section on Neural Developmental Dynamics, Laboratory of Molecular Genetics, NICHD, NIH, Bldg 6B Room 3B 315, 6 Center Drive, Bethesda MD 20892-2785, USA.
Correspondence to: Maikel P. Peppelenbosch1 e-mail: M.P.Peppelenbosch@med.umcg.nl
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