Optogenetic Inhibition of Delta Reveals Digital Notch Signalling Output During Tissue Differentiation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2019 Nov 1

PMID 31668010

Citations 24

Authors

Ranjith Viswanathan

Aleksandar Necakov

Mateusz Trylinski

Rohit Krishnan Harish

Daniel Krueger

Emilia Esposito

Francois Schweisguth

Pierre Neveu

Stefano De Renzis

Affiliations

Soon will be listed here.

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.

Citing Articles

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