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

S.H. Diks; M.A. Sartori da Silva; J.-L. Hillebrands; R.J. Bink; H.H. Versteeg; C. van Rooijen; A.M. Brouwers; A.B. Chitnis; M.P. Peppelenbosch; D. Zivkovic

doi:10.1038/ncb1779

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

S.H. Diks, M.A. Sartori da Silva, J.-L. Hillebrands, R.J. Bink, H.H. Versteeg, C. van Rooijen, A.M. Brouwers, A.B. Chitnis, M.P. Peppelenbosch, D. Zivkovic

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-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 language	English
Pages (from-to)	1190-1198
Journal	Nature Cell Biology
Volume	10
Issue number	10
DOIs	https://doi.org/10.1038/ncb1779
Publication status	Published - 2008

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@article{455b0a551cec4d2abf64f8679d90cc96,

title = "d-Asb11 is an essential mediator of canonical Delta-Notch signalling.",

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.",

author = "S.H. Diks and {Sartori da Silva}, M.A. and J.-L. Hillebrands and R.J. Bink and H.H. Versteeg and {van Rooijen}, C. and A.M. Brouwers and A.B. Chitnis and M.P. Peppelenbosch and D. Zivkovic",

note = "Reporting year: 2008",

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doi = "10.1038/ncb1779",

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journal = "Nature Cell Biology",

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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 -

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

Abstract

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