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Review
, 85 (3), 178-187

Meeting the Meiotic Challenge: Specializations in Mammalian Oocyte Spindle Formation

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Review

Meeting the Meiotic Challenge: Specializations in Mammalian Oocyte Spindle Formation

Ashley L Severance et al. Mol Reprod Dev.

Abstract

Oocytes uniquely accumulate cytoplasmic constituents to support early embryogenesis. This unique specialization is accompanied by acquisition of a large size and by execution of asymmetric meiotic divisions that preserve precious ooplasm through the expulsion of minimal size polar bodies. While often taken for granted, these basic features of oogenesis necessitate unique specializations of the meiotic apparatus. These include a chromatin-sourced RanGTP gradient that restricts spindle size by defining a spatial domain where meiotic spindles form, acentriolar centrosomes that rely on microtubule organizing centers to form spindle poles, and an actin-based mechanism for asymmetric spindle positioning. Additionally, localized protein synthesis to support spindle formation is achieved in the spindle forming region, whilst protein synthesis is reduced elsewhere in the ooplasm. This is achieved through enrichment of spindle-related mRNAs in the spindle forming region combined with local PLK1-mediated phosphorylation and inactivation of the translational repressor EIF4EBP1. This allows PLK1 to function as an important regulatory nexus through which endogenous and exogenous signals can impact spindle formation and function, and highlights the important role that PLK1 may have in maintaining oocyte quality and fertility.

Keywords: EIF4EBP1; aneuploidy; chromosome segregation; meiosis; microtubule nucleation; oocyte meiotic spindle.

Conflict of interest statement

Declarations of Interest

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. RanGTP gradient around MI spindle
At the chromosomes, RCC1 converts RanGDP to RanGTP and diffusion of RanGTP forms the RanGTP gradient. In the cytoplasm, RanGAP converts RanGTP back to RanGDP, setting the boundary for the RanGTP gradient and defining the region for spindle formation in the oocyte.
Figure 2
Figure 2. Oocyte Microtubule Organizing Centers (MTOCs) fragment, migrate, and coalesce to direct meiotic spindle formation
GV oocytes possess few MTOCs that are localized to the nuclear envelope. These MTOCs fragment and stretch around the GV. After germinal vesicle breakdown (GVBD), the MTOCs fragment a second time and then, migrate to opposite sides of the chromosomes, where the spindle poles will form. Lastly, the MTOCs coalesce to form the spindle poles and direct microtubule nucleation and spindle formation.
Figure 3
Figure 3. The actin cytoskeleton controls MI spindle migration and MII spindle tethering to the oocyte cortex
MI oocyte: MI spindle forms slightly off-centered. The different spindle pole-to-cortex distances result in unequal phospho-myosin-II pulling forces on actin and the spindle migrates towards the cortex in the direction of the closer spindle pole. MII oocyte: The small MII spindle forms in close proximity to the cortex in close proximity to where first polar body extrusion occurred. The actin cytoskeleton tethers it tightly to the oocyte cortex.
Figure 4
Figure 4. Model of cap-dependent translation regulation at the meiotic spindle
Top: PLK1 maintains EIF4EBP1 phosphorylation at the meiotic spindle poles, preventing EIF4EBP1 from binding to EIF4E. Therefore, EIF4E and EIF4G are bound, forming the cap-dependent initiation complex and together, they activate translation of RNAs enriched at the meiotic spindle. Bottom: When PLK1 is lost from the spindle, EIF4EBP1 phosphorylation is also lost. EIF4EBP1 binds to EIF4E in place of EIF4G and cap-dependent translation is blocked. The poor supply of spindle-needed proteins to the spindle structure causes a variety of spindle defects on both meiotic spindles. These defects include a decrease in β-tubulin intensity on the MI spindle, and this is illustrated in the bottom figure as thinner black lines. Chromosome congression defects shown were only noted on MI spindles.

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