PT  - JOURNAL ARTICLE
AU  - Ranjith Viswanathan
AU  - Aleksandar Necakov
AU  - Mateusz Trylinski
AU  - Rohit Krishnan Harish
AU  - Daniel Krueger
AU  - Emilia Esposito
AU  - Francois Schweisguth
AU  - Pierre Neveu
AU  - Stefano De Renzis
TI  - Optogenetic inhibition of Delta reveals digital Notch signaling output during tissue differentiation
AID  - 10.1101/738039
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 738039
4099  - http://biorxiv.org/content/early/2019/08/17/738039.short
4100  - http://biorxiv.org/content/early/2019/08/17/738039.full
AB  - 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.