Feedback control of the metaphase-anaphase transition in sea urchin zygotes: role of maloriented chromosomes

To help ensure the fidelity of chromosome transmission during mitosis, sea urchin zygotes have feedback control mechanisms for the metaphase-anaphase transition that monitor the assembly of spindle microtubules and the complete absence of proper chromosome attachment to the spindle. The way in which these feedback controls work has not been known. In this study we directly test the proposal that these controls operate by maloriented chromosomes producing a diffusible inhibitor of the metaphase-anaphase transition. We show that zygotes having 50% of their chromosomes (approximately 20) unattached or monoriented initiate anaphase at the same time as the controls, a time that is well within the maximum period these zygotes will spend in mitosis. In vivo observations of the unattached maternal chromosomes indicate that they are functionally within the sphere of influence of the molecular events that cause chromosome disjunction in the spindle. Although the unattached chromosomes disjoin (anaphase onset without chromosome movement) several minutes after spindle anaphase onset, their disjunction is correlated with the time of spindle anaphase onset, not the time their nucleus breaks down. This suggests that the molecular events that trigger chromosome disjunction originate in the central spindle and propagate outward. Our results show that the mechanisms for the feedback control of the metaphase-anaphase transition in sea urchin zygotes do not involve a diffusible inhibitor produced by maloriented chromosomes. Even though the feedback controls for the metaphase-anaphase transition may detect the complete absence of properly attached chromosomes, they are insensitive to unattached or mono-oriented chromosomes as long as some chromosomes are properly attached to the spindle.