Genes Dev. 31, 524–535 (2017)

Credit: GENES DEV.

Temporal control of gene expression is critical for cellular function and fate determination. Some genes, such as the Notch effector Hes1, exhibit an oscillating pattern of gene expression, marked by rapid mRNA synthesis and degradation due to negative feedback. Optogenetic approaches have enabled the generation of artificial oscillations with rapid spatial–temporal precision, whereas the use of bioluminescent or fluorescent reporters allows detection of oscillations at the single-cell level. However, it is not clear whether this oscillatory information can be transferred to neighboring cells. Isomura et al. developed a combined optogenetic and bioluminescence approach to investigate whether oscillatory information could be communicated between cells. In photosensitive, signal-sending cells, they used a modified version of the LightOn–GAVPO system consisting of the light–oxygen–voltage (LOV) domain protein Vivid (VVD), which forms an active homodimer with the p65 transactivation domain upon blue-light exposure. This complex binds to the upstream activating sequence, driving short-lived expression of the Notch ligand Delta. Delta interacts with the Notch receptor on the neighboring photo-insensitive cell, which contains a destabilized bioluminescent Hes1 reporter and a native oscillator circuit of Hes1. Periodic blue-light exposure of the GAVPO-expressing cells produced Hes1 oscillations in the neighboring cells that were dependent on the length of exposure. Overall, this optogenetic bioluminescence system enables detection of cell–cell communication with spatiotemporal resolution.