Optogenetic inhibition of Delta reveals digital Notch signalling output during tissue differentiation

Abstract: Spatio‐temporal regulation of signalling pathways plays a key role in generating diverse responses during the development of multicellular organisms. The role of signal dynamics in transferring signalling information in vivo is incompletely understood. Here, we employ genome engineering in Drosophila melanogaster to generate a functional optogenetic allele of the Notch ligand Delta (opto‐Delta), which replaces both copies of the endogenous wild‐type locus. Using clonal analysis, we show that optogenetic activation blocks Notch activation through cis‐inhibition in signal‐receiving cells. Signal perturbation in combination with quantitative analysis of a live transcriptional reporter of Notch pathway activity reveals differential tissue‐ and cell‐scale regulatory modes. While at the tissue‐level the duration of Notch signalling determines the probability with which a cellular response will occur, in individual cells Notch activation acts through a switch‐like mechanism. Thus, time confers regulatory properties to Notch signalling that exhibit integrative digital behaviours during tissue differentiation.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Optogenetic inhibition of Delta reveals digital Notch signalling output during tissue differentiation ; volume:20 ; number:12 ; year:2019 ; extent:13
EMBO reports / European Molecular Biology Organization ; 20, Heft 12 (2019) (gesamt 13)

Creator
Viswanathan, Ranjith
Necakov, Aleksandar
Trylinski, Mateusz
Harish, Rohit Krishnan
Krueger, Daniel
Esposito, Emilia
Schweisguth, Francois
Neveu, Pierre
De Renzis, Stefano

DOI
10.15252/embr.201947999
URN
urn:nbn:de:101:1-2022081008533376531893
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:32 AM CEST

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Associated

  • Viswanathan, Ranjith
  • Necakov, Aleksandar
  • Trylinski, Mateusz
  • Harish, Rohit Krishnan
  • Krueger, Daniel
  • Esposito, Emilia
  • Schweisguth, Francois
  • Neveu, Pierre
  • De Renzis, Stefano

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