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Restarting life: fertilization and the transition from meiosis to mitosis

Nature Reviews Molecular Cell Biology volume 14, pages 549–562 (2013)Cite this article

Subjects

Key Points

  • Upon fertilization, two highly specialized meiotic germ cells, the sperm and egg, need to be transformed into a totipotent mitotic embryo.

  • Sperm bind to the zona pellucida of the egg by an unknown mechanism that depends on the cleavage status and oligosaccharide modifications of zona pellucida proteins.

  • Sperm–egg fusion causes a rise in intracellular Ca2+ levels, which triggers exit from meiotic arrest and the initiation of the transition from meiosis to mitosis.

  • Maternal and paternal chromosomes are extensively modified following fertilization to ensure the genome is reprogrammed for totipotency and accurately distributed between daughter cells in the embryo.

  • The transition from meiotic to mitotic spindle assembly occurs gradually during mouse development and involves de novo production of centrioles in the blastocyst.

  • Actin-dependent spindle positioning and microtubule-dependent positioning of pronuclei have important roles in regulating the symmetry of cell division before and after fertilization.

  • The transition from maternal to embryonic control of gene expression involves the regulated degradation of maternal transcripts and timely activation of transcription from the embryonic genome.

Abstract

Fertilization triggers a complex cellular programme that transforms two highly specialized meiotic germ cells, the oocyte and the sperm, into a totipotent mitotic embryo. Linkages between sister chromatids are remodelled to support the switch from reductional meiotic to equational mitotic divisions; the centrosome, which is absent from the egg, is reintroduced; cell division shifts from being extremely asymmetric to symmetric; genomic imprinting is selectively erased and re-established; and protein expression shifts from translational control to transcriptional control. Recent work has started to reveal how this remarkable transition from meiosis to mitosis is achieved.

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Figure 1: From oocyte to embryo.
Figure 2: Fertilization: sperm–egg binding and exit from meiosis.
Figure 3: Transition from meiotic to mitotic chromosomes.
Figure 4: Transition from acentrosomal to centrosomal spindle assembly.
Figure 5: Transition from asymmetric to symmetric spindle positioning.
Figure 6: Regulation of gene expression during egg to embryo transition.

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Acknowledgements

Dean Clift and Melina Schuh have received financial support from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 241548.

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    Dean Clift & Melina Schuh

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Glossary

Zona pellucida

A specialized extracellular matrix that forms a thick coat surrounding the egg.

Polyspermy

An egg is fertilized by more than one sperm.

Tobacco etch virus protease technology

(TEV protease technology). Using this technique, the recognition sequence for the TEV protease is introduced into proteins so that they may be artificially cleaved in vivo by ectopic expression of TEV protease.

APC/C

(Anaphase promoting complex; also known as the cyclosome). An E3 ubiquitin ligase that triggers anaphase by ubiquitylating cyclin B and securin, which targets them for proteolysis by the proteasome.

Separase

A Cys protease that triggers chromosome segregation by cleaving chromosomal cohesin complexes.

Pronucleus

The haploid nucleus of either sperm or egg within the zygote.

Totipotency

The ability of a cell to divide and produce all the differentiated cells of an organism.

Reductional chromosome segregation

During meiosis I, pairs of homologous chromosomes are segregated so that each daughter cell contains half the number of chromosomes as the parent.

Equational chromosome segregation

During meiosis II and mitosis, sister chromatids are segregated so that each daughter cell contains the same number of chromosomes as the parent.

Polysome

A cluster of ribosomes bound to an mRNA molecule, which is indicative of active translation.

N-end rule pathway

An ubiquitin–proteasome proteolysis pathway that regulates the half-life of cellular proteins based on their amino-terminal amino acid residue.

Telocentric

Centromeres located at the ends of chromosomes close to telomeres.

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Clift, D., Schuh, M. Restarting life: fertilization and the transition from meiosis to mitosis. Nat Rev Mol Cell Biol 14, 549–562 (2013). https://doi.org/10.1038/nrm3643

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