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Symmetry breaking, a central principle of physics, has been hailed as thedriver of self-organization in biological systems in general and biogenesis ofcellular organelles in particular, but the molecular mechanisms of symmetrybreaking only begin to become understood. Centrioles, the structural cores ofcentrosomes and cilia, must duplicate every cell cycle to ensure their faithfulinheritance through cellular divisions. Work in model organisms identifiedconserved proteins required for centriole duplication and found that alteringtheir abundance affects centriole number. However, the biophysical principlesthat ensure that, under physiological conditions, only a single procentriole isproduced on each mother centriole remain enigmatic. Here we propose amechanistic biophysical model for the initiation of procentriole formation inmammalian cells. The model faithfully recapitulates the experimentally observedtransition from PLK4 uniformly distributed around the mother centriole, the"ring", to a unique PLK4 focus, the "spot", that triggers the assembly of a newprocentriole. This symmetry breaking requires a dual positive feedback based onautocatalytic activation of PLK4 and enhanced centriolar anchoring of PLK4-STILcomplexes by phosphorylated STIL. We find that, contrary to previous proposals,in situ degradation of active PLK4 is insufficient to break symmetry. Instead,the model predicts that competition between transient PLK4 activity maxima forPLK4-STIL complexes explains both the instability of the PLK4 ring andformation of the unique PLK4 spot. In the model, strong competition atphysiologically normal parameters robustly produces a single procentriole,while increasing overexpression of PLK4 and STIL weakens the competition andcauses progressive addition of procentrioles in agreement with experimentalobservations.

Autoamplification and competition drive symmetry breaking: Initiation of centriole duplication by the PLK4-STIL network