Hunter, Ginger L.Hadjivasiliou, ZenaBonin, HopeHe, LiPerrimon, NorbertCharras, GuillaumeBaum, Buzz2021-10-062016-07-01Hunter, Ginger L., Zena Hadjivasiliou, Hope Bonin, Li He, Norbert Perrimon, Guillaume Charras, Buzz Baum. "Coordinated Control of Notch/Delta Signalling and Cell Cycle Progression Drives Lateral Inhibition-Mediated Tissue Patterning." Development 143, no. 13 (2016): 2305-2310. DOI: 10.1242/dev.1342130950-19911477-9129https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369710Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning.en-USJournal Article2021-10-0610.1242/dev.134213