| RRC ID |
59191
|
| 著者 |
Viswanathan R, Necakov A, Trylinski M, Harish RK, Krueger D, Esposito E, Schweisguth F, Neveu P, De Renzis S.
|
| タイトル |
Optogenetic inhibition of Delta reveals digital Notch signalling output during tissue differentiation.
|
| ジャーナル |
EMBO Rep
|
| 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.
|
| 巻・号 |
20(12)
|
| ページ |
e47999
|
| 公開日 |
2019-12-5
|
| DOI |
10.15252/embr.201947999
|
| PMID |
31668010
|
| PMC |
PMC6893285
|
| MeSH |
Animals
Animals, Genetically Modified
Cell Differentiation
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster / genetics
Drosophila melanogaster / growth & development
Drosophila melanogaster / metabolism*
Genes, Insect
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Membrane Proteins / antagonists & inhibitors*
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mutation
Optogenetics
Phenotype
Receptors, Notch / genetics
Receptors, Notch / metabolism*
Signal Transduction
Spatio-Temporal Analysis
|
| IF |
7.497
|
| 引用数 |
2
|
| リソース情報 |
| ショウジョウバエ |
DGRC#115544 |
