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Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis

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The ability to reproduce relies in most eukaryotes on specialized cells called gametes. Gametes are formed by the process of meiosis in which, after a single round of replication, two successive cell divisions reduce the ploidy of the genome. Fusion of gametes at fertilization reconstitutes diploidy. In most animal species, chromosome segregation during female meiosis occurs on spindles assembled in the absence of the major microtubule-organizing center, the centrosome. In mammals, oocyte meiosis is error prone and underlies most birth aneuploidies. Here, we review recent work on acentrosomal spindle formation and chromosome alignment/separation during oocyte meiosis in different animal models.

Section snippets

Oocyte meiosis is acentrosomal

In most eukaryotic organisms, sexual reproduction relies on a specialized type of cell division termed meiosis that generates a reproduction-specific cell population called gametes. A hallmark of these specialized cells is that they contain a haploid number of chromosomes. This feature is crucial to maintaining the ploidy of sexually reproducing organisms on fertilization, when the paternal gamete (sperm) fuses with the maternal gamete (oocyte). To halve the amount of genetic material, a single

Chromatin can act as an acentrosomal MTOC

The study of acentrosomal spindles has led to significant progress in understanding how and where microtubules are assembled in the absence of centrosomes. In a seminal experiment, DNA-coated beads were shown to support formation of bipolar spindles in cell-free Xenopus egg extracts [10], indicating that chromatin can act as a localized origin for spindle microtubules (Figure 2).

In contrast to frog egg extracts, spindle microtubules in intact vertebrate oocytes do not emanate directly from

The spindle self-organization process

Concomitant with their assembly, microtubules must organize into a bipolar spindle-shaped structure. During mitosis, the two centrosomes mature, split and move toward opposite sides of the nucleus via antiparallel microtubule sliding and/or cortical forces. This mechanism ensures bipolarity of the spindle and imposes a spindle axis before or during rupture of the nuclear envelope. During female meiosis, in the absence of pre-imposed bipolarity, the spindle axis is aligned progressively as

Chromosome alignment and segregation on acentrosomal spindles

Although acentrosomal spindle assembly has been the subject of numerous studies, how these spindles interact with chromosomes is less clear. Spindle microtubules can interact either with motors localized on chromosome arms termed chromokinesins, or with the centromere regions via the kinetochore 46, 47. During mitosis in animal cells, microtubules assembled from the centrosomes grow toward the chromosomes, where they interact with chromosome arms and kinetochores [47]. Whether the same model

Acentrosomal spindles and polar body formation

In most animal species, with the notable exception of Drosophila [67], meiosis I and II end with highly asymmetric divisions leading to the extrusion of half of the segregated chromosome complement into non-dividing polar bodies. These asymmetric divisions depend on the positioning of the acentrosomal spindle in close proximity to the oocyte cortex, which, depending on the species, occurs before or after meiosis I spindle assembly [68].

Concluding remarks

Almost a century after the pioneering work of Van Beneden on meiosis, the molecular mechanisms underlying this specialized cell division are beginning to be elucidated. Here, we have focused on the acentrosomal oocyte meiotic spindle, the assembly and function of which are critical to the formation of the female gamete in animal cells. A key question that remains unanswered is why are centrosomes eliminated in the oocytes of most animal species? A simple answer would be that centrosome

Acknowledgments

This work was supported by grants from the Agence Nationale de la Recherche (ANR-09-RPDOC-005-01) and the Fondation pour la Recherche Médicale to J.D., funding from the Ludwig Institute for Cancer Research and a grant from the National Institutes of Health to A.D. (GM074215). We apologize to our colleagues whose work could not be cited owing to space limitations.

Glossary

Chromokinesin
kinesin that displays a classical microtubule motor domain and a DNA-binding domain.
Fluorescence resonance energy transfer (FRET)
useful light microscopy tool for detecting and quantify protein–protein interactions or conformational changes.
Flux
continuous poleward movement of microtubules due to constant addition of tubulin subunits at microtubule (+)-ends and their corresponding removal from microtubule (–)-ends at spindle poles.
Kinetochore
multiprotein complex that assembles at the

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