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.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Viswanathan R,Necakov A,Trylinski M,Harish RK,Krueger D,Esposito E,Schweisguth F,Neveu P,De Renzis Sdoi
10.15252/embr.201947999subject
Has Abstractpub_date
2019-12-05 00:00:00pages
e47999issue
12eissn
1469-221Xissn
1469-3178journal_volume
20pub_type
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