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Review
. 2015 Jul;67(7):575-87.
doi: 10.1002/iub.1404. Epub 2015 Jul 14.

Splitting the cell, building the organism: Mechanisms of cell division in metazoan embryos

Megha Kumar  1 , Kumari Pushpa  1 , Sivaram V S Mylavarapu  1
Affiliations
Review

Splitting the cell, building the organism: Mechanisms of cell division in metazoan embryos

Megha Kumar et al. IUBMB Life. 2015 Jul.

Abstract

The unicellular metazoan zygote undergoes a series of cell divisions that are central to its development into an embryo. Differentiation of embryonic cells leads eventually to the development of a functional adult. Fate specification of pluripotent embryonic cells occurs during the early embryonic cleavage divisions in several animals. Early development is characterized by well-known stages of embryogenesis documented across animals--morulation, blastulation, and morphogenetic processes such as gastrulation, all of which contribute to differentiation and tissue specification. Despite this broad conservation, there exist clearly discernible morphological and functional differences across early embryonic stages in metazoans. Variations in the mitotic mechanisms of early embryonic cell divisions play key roles in governing these gross differences that eventually encode developmental patterns. In this review, we discuss molecular mechanisms of both karyokinesis (nuclear division) and cytokinesis (cytoplasmic separation) during early embryonic divisions. We outline the broadly conserved molecular pathways that operate in these two stages in early embryonic mitoses. In addition, we highlight mechanistic variations in these two stages across different organisms. We finally discuss outstanding questions of interest, answers to which would illuminate the role of divergent mitotic mechanisms in shaping early animal embryogenesis.

Keywords: cytokinesis; early embryonic development; fate specification; metaphase; metazoa; mitosis; spindle orientation.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Fig 1
Fig 1. Phases of early mitosis.
A: Upon entry into the mitotic phase of cell cycle, an irregular shaped metazoan cell undergoes mitotic rounding and acquires a spherical shape coupled with drastic cytoskeletal reorganization. By prometaphase, the nuclear membrane disintegrates, the centrosomes undergo duplication and migrate to opposite ends, forming the spindle poles. At metaphase, the chromosomes lie in the center of the mitotic spindle. The chromosomes are held at the metaphase plate by the kinetochore microtubules, while the spindle itself is anchored to the cell cortex by astral microtubules. B: At the kinetochore, the minus-end directed dynein-dynactin motor complex transports cargo such as checkpoint proteins (e.g., Mad2) toward the spindle poles, initiating silencing of the checkpoint and entry into anaphase. C: At the polar cell cortex, dynein and the NuMA–LGN–Gαi complex are required for correct positioning and orientation of the mitotic spindle.
Fig 2
Fig 2. Cleavage divisions across metazoa.
A: Representation of spindle positioning from zygote (1 cell) to 8 cell stage in various metazoans. In the one-cell stage C. elegans embryo, the spindle is positioned asymmetrically toward the posterior end, giving rise to daughter cells with different fates. In Drosophila, successive nuclear divisions coupled with the absence of cytokinesis give rise to a syncytial embryo. Sea urchin embryos undergo asymmetric divisions giving rise to micromeres and macromeres. In contrast, early divisions are symmetric in zebrafish embryos. Mouse embryos also undergo asymmetric divisions, giving rise to daughter cells with different cell fates. B: In the one-cell stage C. elegans embryo, the mitotic spindle shifts to the posterior end, giving rise to AB and P1 cells, which again undergo asymmetric divisions. C: During gastrulation in zebrafish, spindles are positioned along the animal-vegetal axis.
Fig 3
Fig 3. Mechanism of cytokinesis in animal cells.
A: Specification of the cytokinetic plane by cues from the mitotic spindle. Aster density limits cortical contractility only to the equator while inhibiting it at the polar cortex. The spindle midzone activates RhoA at the equator upon decline in Cdk1 activity via the Centralspindlin-ECT1 pathway. B: RhoA assembles the actomyosin based contractile ring by activating both actin and myosin at the equatorial plane. C: Furrow contraction and membrane insertion by vesicular trafficking forms a narrow cytoplasmic bridge between the daughter cells, at the center of which lies an electron-dense midbody. D: A secondary constriction mediated by the ESCRT complex appears on either side of the midbody. The microtubule bundle is disassembled by Spastin. E: Finally the ESCRT complex disappears and membrane abscission occurs, separating the two daughter cells.
Fig 4
Fig 4. Variations in cytokinesis during metazoan development.
A: Fertilization-triggered meiotic divisions of the oocyte in C. elegans are extremely asymmetric resulting in polar bodies devoid of cytoplasm and the haploid oocyte retaining most of the cytoplasm. Soon after fertilization, cortical contraction in the C. elegans embryo forms a pseudocleavage that segregates the fate determinants in the zygote, a process that is essential for antero-posterior axis specification. B: Drosophila embryos initially demonstrate a cytokinesis-free nuclear division upto 8 nuclear cycles. At the 9th nuclear division, these nuclei migrate to the periphery and continue to divide without undergoing cytoplasmic divisions for another three cycles. During these peripheral divisions, they form pseudocleavages/partial furrows to shield the chromatin from the influence of neighboring asters. The nuclei finally undergo cellularization at interphase of the 14th nuclear division, utilizing an actomyosin-based contractile machinery similar to conventional cytokinesis.
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