Singularity in polarization: re-wiring yeast cells to make two buds

For migrating cells, budding yeast, and many other cells, it is critical that polarization occur towards one, and only one, site (the singularity rule). Polarity establishment involves amplification of Cdc42 foci via positive feedback, but the basis for singularity was unclear. To assess whether or not singularity is linked to Cdc42 amplification, we disabled the yeast cell’s endogenous amplification mechanism and synthetically re-wired the cells to employ a different positive feedback loop to generate Cdc42 foci. Re-wired cells violated the singularity rule, occasionally making two buds. Mathematical modeling indicated that, given sufficient time, competition between foci would promote singularity. In re-wired cells, slower competition sometimes resulted in a failure to develop a single “winning” focus before budding. Manipulations predicted to slow competition in normal cells also allowed occasional formation of two buds, suggesting that singularity is enforced by rapid competition between Cdc42 foci.