Gould studies oenocytes—a large, secretory cell type in flies that may generate or respond to hormone signals during embryonic moults. Looking at oenocyte specification in real time, Gould's group noticed that cells clustered around a C1 cell—the source of EGFR ligand—in groups of 3, and departed in the same cohorts. Normal animals went through two such pulses of 3 cells arriving and leaving, although overexpression of an EGFR ligand resulted in up to 7 or 8 pulses.
Several downstream targets of EGFR signaling were expressed in far more than the 3 cells immediately around each C1. But the London group found that other critical targets were expressed only in the 3 closest cells thanks to the feedback inhibitor Argos, which turns off signaling in more distant cells receiving intermediate or low levels of EGFR stimulation. Interference with the Argos system eliminated the 3 by 3 nature of the specification process, and resulted in late defects in differentiation.
The grouping of 3 cells per round appears to reflect the geometry of cell packing: that is how many cells fit around a single C1 cell. Argos then ensures that cells further away register no signal rather than a half-hearted signal that might lead to errors. “By delaminating in a pulse-by-pulse mechanism,” says Gould, “it would provide you with a way of regulating exposure to ligand in a more reproducible and regulated manner.” The pulsatile strategy may be used in other signaling systems such as the fly eye, where EGFR stimulation drives stepwise differentiation of photoreceptors.