RT Journal Article
SR Electronic
T1 Optogenetic inhibition of Delta reveals digital Notch signaling output during tissue differentiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 738039
DO 10.1101/738039
A1 Ranjith Viswanathan
A1 Aleksandar Necakov
A1 Mateusz Trylinski
A1 Rohit Krishnan Harish
A1 Daniel Krueger
A1 Emilia Esposito
A1 Francois Schweisguth
A1 Pierre Neveu
A1 Stefano De Renzis
YR 2019
UL http://biorxiv.org/content/early/2019/08/17/738039.abstract
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.