Dev. Cell 10.1016/j.devcel.2017.07.014 (2017)

During Caenorhabditis elegans development, a graded EGFR–Ras–ERK signal is received by the six vulval precursor cells (VPCs). The P6.p cell receives the highest ERK signal, initiating formation of the vulva, whereas the neighboring VPCs, P5.p and P7.p, receive lower levels and adopt the secondary vulval fate. Fluorescent transcriptional reporters to detect ERK activity are limited, owing to the lag time between activation and fluorescence. de la Cova et al. have explored an alternative approach using kinase translocation reporters (KTRs), which translate the ERK phosphorylation status into the nucleocytoplasmic localization of a fluorescent reporter. The authors have modified an established ERK KTR for use in C. elegans by creating a biscistronic transgene containing the ERK KTR with an mCherry-H2B nuclear marker enabling detection of ERK activity by measuring the ratio of red/green signals in the nucleus. Analysis of fluorescence during vulval induction revealed multiple activity pulses in P6.p cells relative to the neighboring VPCs, in agreement with observations of frequency-modulated signaling. Altogether, this sensor system provides an exciting opportunity to detect ERK signaling with improved resolution in C. elegans and a potential to expand to other developmental organisms.