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How germ granules promote germ cell fate

A Publisher Correction to this article was published on 09 July 2024

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Abstract

Germ cells are the only cells in the body capable of giving rise to a new organism, and this totipotency hinges on their ability to assemble membraneless germ granules. These specialized RNA and protein complexes are hallmarks of germ cells throughout their life cycle: as embryonic germ granules in late oocytes and zygotes, Balbiani bodies in immature oocytes, and nuage in maturing gametes. Decades of developmental, genetic and biochemical studies have identified protein and RNA constituents unique to germ granules and have implicated these in germ cell identity, genome integrity and gamete differentiation. Now, emerging research is defining germ granules as biomolecular condensates that achieve high molecular concentrations by phase separation, and it is assigning distinct roles to germ granules during different stages of germline development. This organization of the germ cell cytoplasm into cellular subcompartments seems to be critical not only for the flawless continuity through the germline life cycle within the developing organism but also for the success of the next generation.

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Fig. 1: Summary of germ cell development in various model organisms.
Fig. 2: Embryonic germ granule assembly and substructure.
Fig. 3: Domain structure and assembly hierarchy of select germ granule proteins.
Fig. 4: Oocyte germ granule composition and timing of assembly during oogenesis.
Fig. 5: Perinuclear nuage organization and function in the PIWI-associated RNA (piRNA) pathway.

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Acknowledgements

The authors thank members of the Lehmann laboratory for the critical reading and feedback. The authors apologize to any authors whose work was not cited owing to word limits. Work in the laboratory of the authors on germ cell development has been supported by R01HD110546, R37HD41900 and the Howard Hughes Medical Institute to R.L. and 1F32GM140745-01 to M.C.P.

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M.C.P. and R.L. contributed equally to all aspects of the article.

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Correspondence to Ruth Lehmann.

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Nature Reviews Genetics thanks Elizabeth Gavis, who co-reviewed with Kira Mitchel, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Epistasis

The interaction of genes that are not alleles, in particular the suppression of the effect of one such gene by another, which is used to order gene functions into pathways.

Muller’s ratchet

A theory predicting that small asexual populations invariably accumulate deleterious mutation loads as a consequence of genetic drift, mutations and a lack of recombination.

P-bodies

Membraneless, cytoplasmic ribonucleoprotein cell compartments enriched in enzymes involved in mRNA turnover and translationally repressed mRNA.

Phase separation

A process in biology in which a well-mixed solution of molecules separates (demixes) into two coexisting phases, with one phase being denser (higher molecular concentration) than the other.

Stress granules

Membraneless, cytoplasmic ribonucleoprotein cell compartments that form in response to different cellular stress stimuli.

Transposons

Mobile genetic elements that are capable of cyclic self-excision and insertion in the genome of their host.

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Pamula, M.C., Lehmann, R. How germ granules promote germ cell fate. Nat Rev Genet (2024). https://doi.org/10.1038/s41576-024-00744-8

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