A shift from kinesin 5-dependent metaphase spindle function during preimplantation development in mouse.

Microtubules within meiotic and mitotic spindles continually move towards spindle poles in a process termed poleward flux, which is essential for spindle integrity and faithful chromosome segregation. Kinesin 5 is a longstanding candidate for a molecular motor that might drive poleward flux, and has been shown to drive flux and to be necessary for spindle bipolarity in Xenopus egg extracts. However, kinesin 5 is not necessary for poleward flux or for maintaining metaphase spindle bipolarity in intact mammalian cells, and the reason for the different results in these systems is unknown. The experiments presented here test the hypothesis that these results might reflect developmental differences in spindle function by examining the role of kinesin 5 in mouse eggs and preimplantation embryos. In contrast to cultured somatic cells, poleward flux in mouse eggs is critically dependent upon kinesin 5. Inhibition of poleward flux leads to spindle shortening as a result of continued microtubule depolymerisation at the pole, and eventual loss of spindle bipolarity. Spindle bipolarity is also dependent upon kinesin 5 during the first three embryonic cleavages, but becomes kinesin 5-independent in the majority of spindles by the blastocyst stage. This switch occurs asynchronously in different blastomeres but is independent of clonal cell heritage and of whether the blastomere is within the inner cell mass or the trophoectoderm. These experiments reveal a novel developmental switch in the requirements for spindle function and chromosome segregation during preimplantation development.