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To cite this version:
Adel Al Jord, Marie-Hélène Verlhac. Spindle Assembly: Two Spindles for Two Genomes in a Mam- malian Zygote. Current Biology - CB, Elsevier, 2018, 28, pp.R948 - R951. �10.1016/j.cub.2018.07.044�.
�hal-03003485�
mating mate choice, with males choosing to defend or consume offspring based on clutch size and perhaps other factors.
What role do females play in inhibiting or encouraging ‘filial cannibalism’, and what mechanisms are involved in a father’s switch from protector to predator?
Selection plainly favors females that lay large clutches, but there may also be an opportunity for females to manipulate male behavior through egg chemistry — both in terms of suppressing androgens and discouraging destruction.
Selection also should favor females that can anticipate the probability of clutch destruction. While early studies suggested that females could use courtship vigor as a reliable cue of male nutritional state, and therefore risk of cannibalism[18], Matsumotoet al.’s work [9]suggests that vigorous courtship may, if anything, signal a male who’s recently devoured his progeny. The importance of clutch size for male decisions suggests a tough choice for females: perhaps they maximize clutch survival by entrusting most of their reproductive output to one male, rather than hedging their bets across fathers[19].
Blennies show mutual mate choice:
females by selecting males with whom to oviposit, and males by clutch destruction.
Biological market theory[20]may prove useful in elucidating how mating
outcomes are distributed in systems with male parental care. We gain a much richer picture of behavioral evolution when we consider underlying mechanisms in all parties involved, and when we emancipate these mechanisms from semantic stereotypes.
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Biological markets. Trends Ecol. Evol.10, 336–339.
Spindle Assembly: Two Spindles for Two Genomes
in a Mammalian Zygote
Adel Al Jord*and Marie-Hele`ne Verlhac
CIRB, Colle`ge de France, and CNRS-UMR7241 and INSERM-U1050, Equipe Labellisee FRM, Paris F-75005, France
*Correspondence:[email protected] https://doi.org/10.1016/j.cub.2018.07.044
A single bipolar spindle was thought to form around both parental genomes in zygotes initiating the first division. A recent study challenges this predominant view by showing that two independent spindles assemble to prevent parental genome mixing in mouse zygotes.
The one-cell embryo, or zygote, results from the fusion of male and female haploid gametes. It is a unique state in the life of an organism, as the subsequent encounter of the two parental genomes
within this single cell enables the recovery of a diploid genome. In many model systems, the process starts with the migration of the two pronuclei, each containing a single parental genome, to R948 Current Biology28, R931–R951, September 10, 2018ª2018 Elsevier Ltd.
the centre of the one-cell embryo[1]. The nuclear envelopes surrounding each of the pronuclei then break down before condensed chromosomes congress on a single metaphase plate. In rodents, as opposed to other species including humans[2], the sperm does not contribute centrioles[3,4]. These microtubule-based organelles form de novoduring the ensuing stages of pre- implantation development[5,6]. Spindle assembly in the zygote hence relies on discrete acentriolar microtubule- organising centres (aMTOCs), composed of maternal pericentriolar material, in addition to chromosome-based microtubule nucleation[7]. Despite the developmental significance, how the zygotic spindle gathers chromosomes from the apposed pronuclei remained unclear. Previous studies suggested that the process would resemble that which occurs in oocytes, with a progressive sorting of aMTOCs around the two parental genomes[7–9]. A recent paper in Sciencefrom Reichmannet al.[10]now presents convincing data suggesting otherwise: the authors demonstrate that
each parental chromosomal set assembles its own spindle and the two spindles subsequently fuse to properly segregate chromosomes between the two daughter cells, termed blastomeres.
Moreover, the two genomes remain separated, even after spindle fusion, during the complete course of the zygotic division. This finding complements previous reports highlighting the separation of parental genomes in the early embryo[11,12].
By coupling light-sheet microscopy with differential labelling of parental centromeric DNA sequences, the authors followed the dynamics of male and female chromosomes at high spatiotemporal resolution during the first zygotic division (Figure 1). Embryos coming from aMus musculus–Mus spretuscross were used to distinguish parental chromosomes based on species-specific differences in sequence and abundance of major and minor satellite repeats, as previously reported by others[12,13]. A separation of maternal and paternal genomes was observed from nuclear envelope breakdown until late anaphase of the
mitotic zygote. To understand the origin of this persistent separation, Reichmann et al.[10]documented the assembly of the acentrosomal spindle at these key stages. Countering previous
assumptions, they revealed that each of the two parental chromosome sets assembles its own spindle in
prometaphase (Figure 1). Consistent with the live recordings, cold-stable
endogenous microtubules were also found to be organized into two separate arrays in fixed embryos. Chromosome- and microtubule-tracking experiments then revealed a functional independence of the two spindles relative to
chromosome congression. The two spindles eventually aligned and combined, or fused, prior to anaphase onset, while the two parental sets of chromosomes remained separated (Figure 1).
The authors then postulated that defects in aligning the two spindles may lead to zygotic division errors. To test this hypothesis, they targeted microtubules, which are required for the final merging of parental pronuclei[14]. Transient
Microtubules aMTOC
Maternal chromosome Paternal chromosome Apposed pronuclei
undergo NEBD
Two spindles around
each genome Spindle fusion
Broken nuclear envelope Anaphase Nuclei reformation
Current Biology
Figure 1. Maternal and paternal chromosomes assemble their own spindle in the mouse zygote.
The diagram illustrates how maternal (pink) and paternal (blue) chromosomes are segregated during the first mitosis of the mouse embryo. Acentriolar microtubule-organising centres (aMTOCs) are shown in orange, and microtubules in green. NEBD, nuclear envelope breakdown. The one-cell zygote is presented on the left, the two-cell embryo on the right, and a magnification of the different stages of the first mitosis is shown in the dotted box in the centre.
Current Biology28, R931–R951, September 10, 2018 R949
M-phase entry increased the distance between the two pronuclei and enlarged the gap between the two parental spindles, reducing the efficiency of chromosome segregation. In line with their hypothesis, the authors notably documented the subsequent formation of aberrant multinucleated two-cell embryos, a condition frequently observed inin vitrofertilization clinics[15].
Next, Reichmannet al.[10]assessed a potential mechanistic link between dual- spindle assembly and parental genome separation in zygotes. By following successive divisions of the early embryo, they first found that parental genomes are separated only in zygotes, all of which undergo dual-spindle assembly. Indeed, maternal and paternal chromosome sets started mixing as of metaphase at the two-cell stage and in the presence of a single common spindle. To confirm the dependence of parental genome mixing on the organization of one spindle, the authors artificially redirected spindle assembly in zygotes using a small- molecule inhibitor approach. Transient treatment with monastrol — a kinesin-5 inhibitor[16]that induces the formation of monopolar spindles in early embryonic cleavages[9]— followed by a nocodazole washout allowed the authors to reform a single spindle instead of a dual spindle in the zygote. This experimental approach provoked the mixing of maternal and paternal chromosomes in the zygote, presumably driven by the reformation of a single bipolar spindle after nocodazole washout. The authors did not observe any effect on dual-spindle assembly after the reverse treatment — nocodazole followed by monastrol washout — and, consistently, parental genomes remained separated. These collective results provide a solid link between dual-spindle assembly in the zygote and parental genome separation.
The sex-specific DNA-methylation patterns in gametes, along with divergent chromatin composition between the oocyte and sperm, are prime sources of parental asymmetry after fertilization[17].
Whether the physical separation of genomes during the zygotic division participates in propagating or amplifying this initial asymmetry, which is key to the deposition of genomic imprints and certainly essential to mammalian
issue. The experimental set-up of parental genome mixing allowed Reichmannet al.
[10]to test this hypothesis using immunofluorescence labelling of sex- specific epigenetic marks[18]. The authors did not observe a change in signal volume in two- and eight-cell embryos, regardless of whether the parental chromosomes in zygotes were assembled on dual spindles or on an artificially induced single spindle. Indeed, mixing the genomes in the zygote did not perturb the epigenomes, suggesting that the physical separation of parental genomes is not a pre-requisite for sex- specific epigenetic asymmetry in the early embryo. Distinct inherent features of gametic origin could be sufficient to distinguish the two sets of chromosomes.
The work of Reichmannet al.[10]
illuminates with high spatiotemporal resolution the spindle-assembly dynamics in early murine embryos.
However, numerous unknowns remain to be addressed. After fertilization, does the zygote coordinate the migration of pronuclei to the centre of the zygote — a process dependent on F-actin[14]— with M-phase entry and dual-spindle
formation? Such a coordination may help to prevent the observed errors in embryonic development, principally the nucleus tally aberrations. Although the authors linked these errors with defects in the fusion of the two parental spindles, the mechanism behind this fusion process has yet to be identified. Could proteins involved in extra-centrosome clustering, such as HSET[19], the levels of which dramatically increase between meiosis and the first embryonic mitosis[20], be implicated in merging the parental spindles? The authors also report that the physiological dual spindle and the induced single spindle in the zygote lead to the birth of surprisingly comparable amounts of live pups. This unexpected finding suggests that the final outcome of embryogenesis is not impacted by forced genome mixing in the zygote. However, this finding may also just be a
consequence of laboratory breeding conditions that do not necessarily reflect natural environments.
Ultimately, the study by Reichmann et al.[10]could influence legislation and policy elaboration as the zygotic fusion of pronuclei often defines the beginning of
show that mouse embryos fuse parental genomes only as of the two-cell stage of embryogenesis, investigation spindle assembly dynamics in human zygotes is of prime interest. Nevertheless, spindle dynamics in human zygotes could differ from the mouse, considering that human zygotes inherit paternal centrioles[2], which is not the case in acentriolar rodent ones. Thus, additional studies are required to specify whether other mammals, especially humans, deploy a mouse-like mode of spindle assembly in the zygote.
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Current Biology28, R931–R951, September 10, 2018 R951
