The RESTRICTION checkpoint: a window of opportunity governing developmental transitions in Toxoplasma gondii

•The developmental fate of Toxoplasma gondii is decided at the G1 RESTRICTION checkpoint (R-point).•The G1 elongation creates a window of opportunity to integrate cues into developmental changes.•Specific host signals direct development of the multipotent bradyzoites at the R-point.•The inherent heterogeneity of individual bradyzoites is a direct consequence of cell cycle reconstruction. The life cycle of Toxoplasma gondii is characterized by active replication alternating with periods of rest. Encysted dormant sporozoites and bradyzoites initiate active replication as tachyzoites and merozoites. Here we explore the role of the cell cycle with a focus on the canonical G1 RESTRICTION checkpoint (R-point) as the integrator governing developmental decisions in T. gondii. This surveillance mechanism, which licenses replication, creates a window of opportunity in G1 for cellular reorganization in the execution of developmental transitions. We also explore the unique status of the bradyzoite, the only life cycle stage executing both a forward (entry into the sexual cycle) and reverse (recrudescence) developmental transitions as a multipotent cell. These opposing decisions are executed through the common machinery of the RESTRICTION checkpoint.