Abstract
Mitotic spindles assemble from two centrosomes, which are major microtubule‐organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes, however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated from multiple acentriolar MTOCs that are sorted and clustered prior to completion of spindle assembly in an “inside‐out” mechanism, ending with establishment of the poles. We used HSET (kinesin‐14) as a tool to shift meiotic spindle assembly toward a mitotic “outside‐in” mode and analyzed the consequences on the fidelity of the division. We show that HSET levels must be tightly gated in meiosis I and that even slight overexpression of HSET forces spindle morphogenesis to become more mitotic‐like: rapid spindle bipolarization and pole assembly coupled with focused poles. The unusual length of meiosis I is not sufficient to correct these early spindle morphogenesis defects, resulting in severe chromosome alignment abnormalities. Thus, the unique “inside‐out” mechanism of meiotic spindle assembly is essential to prevent chromosomal misalignment and production of aneuploidy gametes.
Highlights
Animal cells generally assemble mitotic spindles using an “outside-in” mechanism that relies on centrosomes acting as dominant microtubule-nucleating centers (MTOCs)
We found that endogenous HSET is localized on the spindle in meiosis I (Fig EV1A, left panel)
We have shown that HSET levels must be tightly gated during meiosis I and that deregulation of HSET amount can be used as a tool to force spindle morphogenesis to be more mitotic-like in several aspects: accelerated kinetics of spindle bipolarization and spindle pole assembly coupled with focused poles
Summary
Animal cells generally assemble mitotic spindles using an “outside-in” mechanism that relies on centrosomes acting as dominant microtubule-nucleating centers (MTOCs). Microtubules are nucleated from chromatin and multiple acentriolar microtubule-organizing centers (aMTOCs) composed of pericentriolar material [6,7,8,9]. These aMTOCs are perinuclear before meiotic divisions and fragment at NEBD (nuclear envelope breakdown) to become evenly distributed around chromatin [10,11]. Following NEBD, microtubules become nucleated and stabilized first around chromatin, forming a microtubule ball, and organized into a stable central array via microtubule motors and microtubule-associated proteins, which sort and orient the microtubules [12,13,14,15,16,17].
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