Binary decision between asymmetric and symmetric cell division is defined by the balance of PAR proteins in C. elegans embryos

Coordination between cell differentiation and proliferation during development requires the balance between asymmetric and symmetric modes of cell division. However, the cellular intrinsic cue underlying the binary choice between these two division modes remains elusive. Here we show evidence in Caenorhabditis elegans that the invariable lineage of the division modes is programmed by the balance between antagonizing complexes of partitioning-defective (PAR) proteins. By uncoupling unequal inheritance of PAR proteins from that of fate determinants during zygote division, we demonstrated that changes in the balance between PAR-2 and PAR-6 are sufficient to re-program the division modes from symmetric to asymmetric and vice versa in two-cell stage embryos. The division mode adopted occurs independently of asymmetry in cytoplasmic fate determinants, cell-size asymmetry, and cell-cycle asynchrony between the sister cells. We propose that the balance between antagonizing PAR proteins represents an intrinsic self-organizing cue for binary specification of the division modes during development.