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

TY - JOUR

T1 - d-Asb11 is an essential mediator of canonical Delta-Notch signalling.

AU - Diks, S.H.

AU - Sartori da Silva, M.A.

AU - Hillebrands, J.-L.

AU - Bink, R.J.

AU - Versteeg, H.H.

AU - van Rooijen, C.

AU - Brouwers, A.M.

AU - Chitnis, A.B.

AU - Peppelenbosch, M.P.

AU - Zivkovic, D.

N1 - Reporting year: 2008

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1038/ncb1779

DO - 10.1038/ncb1779

M3 - Article

SN - 1465-7392

VL - 10

SP - 1190

EP - 1198

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 10

ER -